[ { "id": "https://authors.library.caltech.edu/records/ykqkj-ajy29", "eprint_id": 85216, "eprint_status": "archive", "datestamp": "2023-08-19 08:19:12", "lastmod": "2024-01-14 19:31:34", "type": "book_section", "metadata_visibility": "show", "creators": { "items": [ { "id": "Dervan-P-B", "name": { "family": "Dervan", "given": "Peter B." }, "orcid": "0000-0001-8852-7306" }, { "id": "Kurmis-A-A", "name": { "family": "Kurmis", "given": "Alexis A." } }, { "id": "Finn-P-B", "name": { "family": "Finn", "given": "Paul B." } } ] }, "title": "Molecular Recognition of DNA by Py\u2013Im Polyamides: From Discovery to Oncology", "ispublished": "unpub", "full_text_status": "restricted", "note": "\u00a9 2018 The Royal Society of Chemistry. \n\nPrint publication date: 12 Mar 2018. \n\nWe are grateful to our coworkers and collaborators for their splendid efforts in the research described. We thank also the National Institutes of Health GM27681-38, the American Cancer Society, and the Prostate Cancer Foundation for financial support of this research.", "abstract": "The development of Py\u2013Im polyamides as potential therapeutic agents is an example of the application of fundamental science at all levels from initial concept, based on purely chemical considerations of DNA\u2013binding, through refinement of the design process to improvements in synthesis, critical analysis of DNA\u2013binding properties, solving problems of cell uptake and distribution, pharmacokinetics and whole\u2013animal studies leading up to clinical trials. This chapter will document the story with particular regard to the development of drugs aimed at treating one of the most prevalent cancers that beset patients today, therapy-resistant prostate cancer.", "date": "2018-03-12", "date_type": "published", "publisher": "Royal Society of Chemistry", "place_of_pub": "Cambridge", "pagerange": "298-331", "id_number": "CaltechAUTHORS:20180309-073102749", "isbn": "978-1-78262-992-4", "book_title": "DNA-targeting Molecules as Therapeutic Agents", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20180309-073102749", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "GM27681-38" }, { "agency": "American Cancer Society" }, { "agency": "Prostate Cancer Foundation" } ] }, "contributors": { "items": [ { "id": "Waring-M-J", "name": { "family": "Waring", "given": "Michael J." } } ] }, "doi": "10.1039/9781788012928-00298", "resource_type": "book_section", "pub_year": "2018", "author_list": "Dervan, Peter B.; Kurmis, Alexis A.; et el." }, { "id": "https://authors.library.caltech.edu/records/4dg99-08q78", "eprint_id": 66762, "eprint_status": "archive", "datestamp": "2023-08-22 03:05:35", "lastmod": "2024-01-13 16:50:42", "type": "book_section", "metadata_visibility": "show", "creators": { "items": [ { "id": "Dervan-P-B", "name": { "family": "Dervan", "given": "Peter B." }, "orcid": "0000-0001-8852-7306" }, { "id": "Poulin-Kerstien-A-T", "name": { "family": "Poulin-Kerstien", "given": "Adam T." } }, { "id": "Fechter-E-J", "name": { "family": "Fechter", "given": "Eric J." } }, { "id": "Edelson-B-S", "name": { "family": "Edelson", "given": "Benjamin S." } } ] }, "title": "Regulation of gene expression by synthetic DNA-binding ligands", "ispublished": "unpub", "full_text_status": "restricted", "keywords": "polyamide; DNA; gene regulation", "note": "\u00a9 2005 Springer. \n\nWe are grateful to the National Institutes of Health for research support. A.T.P.-K. is supported by an NIH Predoctoral Training Grant. E.J.F. is supported by an NIH Research Service Award and Ralph M. Parsons Fellowship. B.S.E. is supported by a predoctoral fellowship from the Howard Hughes Medical Institute.", "abstract": "During the past 20 years, polyamides have evolved from the natural product distamycin to a new class of programmable heterocyclic oligomers that bind a broad repertoire of DNA sequences with high affinity and specificity. This chapter details recent advances in this field of research, focusing on molecular recognition of DNA, and biological applications such as modulating gene expression by small molecules. Work presented here represents efforts towards the modulation of specific cellular function by small molecules in an addressable fashion within the context of live cells.", "date": "2005-01-27", "date_type": "published", "publisher": "Springer-Verlag Berlin", "place_of_pub": "Berlin", "pagerange": "1-31", "id_number": "CaltechAUTHORS:20160509-112818968", "isbn": "978-3-540-22835-6", "book_title": "DNA Binders and Related Subjects", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20160509-112818968", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH Predoctoral Fellowship" }, { "agency": "Ralph M. Parsons Foundation" }, { "agency": "Howard Hughes Medical Institute (HHMI)" } ] }, "contributors": { "items": [ { "id": "Waring-M-J", "name": { "family": "Waring", "given": "Michael J." } }, { "id": "Chaires-J-B", "name": { "family": "Chaires", "given": "Jonathan B." } } ] }, "doi": "10.1007/b100440", "resource_type": "book_section", "pub_year": "2005", "author_list": "Dervan, Peter B.; Poulin-Kerstien, Adam T.; et el." }, { "id": "https://authors.library.caltech.edu/records/47s5k-kxh45", "eprint_id": 67186, "eprint_status": "archive", "datestamp": "2023-08-22 01:20:34", "lastmod": "2023-10-18 20:55:54", "type": "book_section", "metadata_visibility": "show", "creators": { "items": [ { "id": "Dervan-P-B", "name": { "family": "Dervan", "given": "Peter B." }, "orcid": "0000-0001-8852-7306" }, { "id": "Fechter-E-J", "name": { "family": "Fechter", "given": "Eric J." } }, { "id": "Edelson-B-S", "name": { "family": "Edelson", "given": "Benjamin S." } }, { "id": "Gottesfeld-J-M", "name": { "family": "Gottesfeld", "given": "Joel M." } } ] }, "title": "Regulation of gene expression with pyrrole-imidazole polyamides", "ispublished": "unpub", "full_text_status": "restricted", "keywords": "gene expression; regulation; inhibition; pyrrole-imidazole polyamides; pairing rules; hairpin motif; cycle motif; binding site size; \u03b2-alanine; solid phase methods; gene activation; nucleosomes; nuclear uptake; DNA detection", "note": "\u00a9 2004 Wiley-VCH. \n\nWe are grateful to the National Institutes of Health for research support. E. J. F. is supported by an NIH Research Service Award and a Ralph M. Parsons Fellowship. B. S. E. is supported by a pre-doctoral fellowship from the Howard Hughes Medical Institute.", "abstract": "The natural product distamycin contains three N-methylpyrrole amino acids and binds in the minor groove of DNA at A,T tracts 4-5 base pairs (bp) in size. Distamycin inhibits DNA-dependent processes, including transcription, and has antibacterial, antimalarial, antifungal and antiviral activities, but is of limited use because of toxicity. Efforts to bring distamycin analogs to the clinic have focused on anti-infective therapeutics. These compounds have been optimized for pathogen activity and pharmacological properties, with DNA binding specificity not providing a major driving force in ligand selection. \n\nDickerson, Rich and Wemmer revealed by X-ray and NMR structural studies that the crescent-shaped molecule could bind A,T tracts in both 1:1 and 2:1 ligand:DNA stoichiometries. Informed by these structures, we explored whether designed distamycin analogs could be tuned by chemical modification in a predictable fashion to bind to a very large number of different DNA sequences, i.e. create an artificial small molecule language to read the minor groove digitally, similar in function to nature's proteins. This might underpin a rational chemical approach to the regulation of gene expression by chemical methods. \n\n\nAfter a 20 year search, we demonstrated that synthetic analogs pf the N-methylpyrrole (Py) carboxamide ring afford a set of heterocycles that can be combined -- as unsymmetrical ring pairs -- in a modular fashion to recognize specifically a large repertoire of DNA sequences with affinities and specificities comparable to DNA-binding proteins. In this chapter we describe advances in the field of DNA-binding polyamides, cellular and nuclear uptake properties and recent biological applications.", "date": "2004", "date_type": "published", "publisher": "Wiley-VCH", "place_of_pub": "Weinheim", "pagerange": "121-152", "id_number": "CaltechAUTHORS:20160519-124154093", "isbn": "9783527306336", "book_title": "Pseudo-Peptides in Drug Development", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20160519-124154093", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH Predoctoral Fellowship" }, { "agency": "Ralph M. Parsons Foundation" }, { "agency": "Howard Hughes Medical Institute (HHMI)" } ] }, "contributors": { "items": [ { "id": "Nielsen-P-E", "name": { "family": "Nielsen", "given": "Peter E." } } ] }, "doi": "10.1002/3527601902.ch3", "resource_type": "book_section", "pub_year": "2004", "author_list": "Dervan, Peter B.; Fechter, Eric J.; et el." }, { "id": "https://authors.library.caltech.edu/records/xgr6n-kw695", "eprint_id": 66824, "eprint_status": "archive", "datestamp": "2023-08-19 07:02:31", "lastmod": "2024-01-13 16:50:44", "type": "book_section", "metadata_visibility": "show", "creators": { "items": [ { "id": "Trauger-J-W", "name": { "family": "Trauger", "given": "John W." } }, { "id": "Dervan-P-B", "name": { "family": "Dervan", "given": "Peter B." }, "orcid": "0000-0001-8852-7306" } ] }, "title": "Footprinting methods for analysis of pyrrole-imidazole polyamide/DNA complexes", "ispublished": "unpub", "full_text_status": "restricted", "note": "\u00a9 2001 Academic Press. \n\nWe are grateful to the National Institutes of Health (General Medical) and the National Foundation for Cancer Research for research support, and to the National Science Foundation and the Ralph M. Parsons Foundation for predoctoral fellowships to J.W.T.", "abstract": "This chapter describes three complementary footprinting methods and the protocols used for analysis of polyamide : DNA complexes: (1) MPE\u2013Fe(II) footprinting, (2) affinity cleavage, and (3) quantitative DNase I footprint titration. Footprinting with methidiumpropyl\u2013EDTA\u2013Fe(II) [MPE\u2013Fe(II)] is used to identify high-affinity polyamide-binding sites to near nucleotide resolution. Affinity cleavage is used to determine the orientation of the bound polyamide in the minor groove of DNA. Quantitative DNase I footprinting is used to determine equilibrium association constants (K_a) for polyamide\u2013DNA complexes at previously identified match and mismatch sites. A pivotal step in the discovery\u2014evaluation process of new polyamide motifs is the characterization of the affinity and specificity of next-generation molecules following the design-sythesis phase. In the design phase, it is often the case that the sequence preference, as well as the energetics of any new molecule binding at each potential site, is not perfectly understood and it is crucial to scan \"libraries\" of many potential DNA-binding sites in order to identify true high-affinity binding sites.", "date": "2001", "date_type": "published", "publisher": "Academic Press", "place_of_pub": "San Diego, CA", "pagerange": "450-466", "id_number": "CaltechAUTHORS:20160510-082727863", "isbn": "9780121822415", "book_title": "Drug-Nucleic Acid Interactions", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20160510-082727863", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH" }, { "agency": "National Foundation for Cancer Research" }, { "agency": "NSF" }, { "agency": "Ralph M. Parsons Foundation" } ] }, "contributors": { "items": [ { "id": "Chaires-J-B", "name": { "family": "Chaires", "given": "Jonathan B." } }, { "id": "Waring-M-J", "name": { "family": "Waring", "given": "Michael J." } } ] }, "doi": "10.1016/S0076-6879(01)40436-8", "resource_type": "book_section", "pub_year": "2001", "author_list": "Trauger, John W. and Dervan, Peter B." }, { "id": "https://authors.library.caltech.edu/records/fcnga-ytc54", "eprint_id": 67188, "eprint_status": "archive", "datestamp": "2023-08-19 07:02:39", "lastmod": "2024-01-13 16:51:28", "type": "book_section", "metadata_visibility": "show", "creators": { "items": [ { "id": "Dervan-P-B", "name": { "family": "Dervan", "given": "Peter B." }, "orcid": "0000-0001-8852-7306" }, { "id": "Urbach-A-R", "name": { "family": "Urbach", "given": "Adam R." } } ] }, "title": "The importance of \u03b2-alanine for recognition of the minor groove of DNA", "ispublished": "unpub", "full_text_status": "restricted", "keywords": "recognition of the minor groove of DNA, \u03b2-alanine", "note": "\u00a9 2001 Verlag Helvetica Chimica Acta. \n\nWe are grateful to the National Institutes of Health for support.", "abstract": "It is now well-recognized that there are two global motifs for targeting the minor groove of DNA based on analogs of the N-methylpyrrole-carboxamide ring of the natural product distamycin. There exist 1:1 and 2:1 stoichiometries with quite different rules of recognition and specificity. This ambiguity of sequence targeting depending on stoichiometry raises a serious design issue for the DNA recognition field.", "date": "2001", "date_type": "published", "publisher": "Verlag Helvetica Chimica Acta", "place_of_pub": "Z\u00fcrich, Switzerland", "pagerange": "327-339", "id_number": "CaltechAUTHORS:20160519-124235592", "isbn": "9783906390284", "book_title": "From Molecular Structure towards Biology", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20160519-124235592", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH" } ] }, "contributors": { "items": [ { "id": "Quinkert-G", "name": { "family": "Quinkert", "given": "Gerhard" } }, { "id": "Kisak\u00fcrek-M-V", "name": { "family": "Kisak\u00fcrek", "given": "M. Volkan" } } ] }, "doi": "10.1002/9783906390451.ch9", "resource_type": "book_section", "pub_year": "2001", "author_list": "Dervan, Peter B. and Urbach, Adam R." }, { "id": "https://authors.library.caltech.edu/records/x0x5g-sdx13", "eprint_id": 66930, "eprint_status": "archive", "datestamp": "2023-08-20 02:10:01", "lastmod": "2024-01-13 16:50:46", "type": "book_section", "metadata_visibility": "show", "creators": { "items": [ { "id": "Iverson-B-L", "name": { "family": "Iverson", "given": "Brent L." } }, { "id": "Dervan-P-B", "name": { "family": "Dervan", "given": "Peter B." }, "orcid": "0000-0001-8852-7306" } ] }, "title": "Adenine-specific DNA chemical sequencing reaction", "ispublished": "unpub", "full_text_status": "restricted", "note": "\u00a9 1993 Academic Press. \n\nWe are grateful to the American Cancer Society for support of this research and for a National Research Service Award to B.L.I. from the National Institute of General Medical Sciences.", "abstract": "DNA sequence determination according to the method of Maxam and Gilbert utilizes base-specific chemical modification reactions followed by a workup that causes cleavage of the sugar-phosphate backbone at the site of the modified base. Reactions have been reported that are capable of selective cleavage of DNA at G, G + A, A > G, A > C, C, C + T, and T residues. We describe here a simple protocol specific for adenine (A) that may be a useful addition to current chemical sequencing reactions. Reaction of DNA with K_2PdC1_4 at pH 2.0 followed by heating in the presence of piperidine produces an A-specific DNA cleavage reaction. The K_2PdCI_4 reaction involves selective depurination at adenine, affording an excision reaction analogous to the other chemical DNA sequencing reactions.", "date": "1993", "date_type": "published", "publisher": "Academic Press", "place_of_pub": "San Diego, CA", "pagerange": "222-227", "id_number": "CaltechAUTHORS:20160510-140053565", "isbn": "978-0-12-182119-7", "book_title": "Recombinant DNA", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20160510-140053565", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "American Cancer Society" }, { "agency": "NIH Predoctoral Fellowship" } ] }, "contributors": { "items": [ { "id": "Wu-Ray", "name": { "family": "Wu", "given": "Ray" } } ] }, "doi": "10.1016/0076-6879(93)18017-7", "resource_type": "book_section", "pub_year": "1993", "author_list": "Iverson, Brent L. and Dervan, Peter B." }, { "id": "https://authors.library.caltech.edu/records/cg6kb-we205", "eprint_id": 66952, "eprint_status": "archive", "datestamp": "2023-08-20 00:51:16", "lastmod": "2024-01-13 16:50:48", "type": "book_section", "metadata_visibility": "show", "creators": { "items": [ { "id": "Strobel-S-A", "name": { "family": "Strobel", "given": "S. A." } }, { "id": "Dervan-P-B", "name": { "family": "Dervan", "given": "P. B." }, "orcid": "0000-0001-8852-7306" } ] }, "title": "Triple helix-mediated single-site enzymatic cleavage of megabase genomic DNA", "ispublished": "unpub", "full_text_status": "restricted", "note": "\u00a9 1992 Elsevier Inc. \n\nWe are grateful to Dr. John Hanish for helpful discussions, the National Institutes of Health for grant support, and the Howard Hughes Medical Institute for a predoctoral fellowship to S.A.S.", "abstract": "This chapter explains the triple helix-mediated single-site enzymatic cleavage of megabase genomic DNA. Oligonucleotide-directed triple helix formation is a generalizable chemical approach for the recognition and cleavage of a single target site within several megabase pairs of duplex genomic DNA. The generalizability of triple helix-mediated enzymatic cleavage affords high specificity that can be readily customized to unique genetic markers without artificial insertion of a target sequence. Extensive sequencing to identify target sites could be avoided by using degenerate oligonucleotides to screen genetic markers for overlapping triple helix/ endonuclease sites. The potential generalizability of triple helix-mediated Achilles' heel cleavage, a technique capable of near-quantitative cleavage at a single site in at least 14 megabase pairs of DNA, could assist in physical mapping of chromosomal DNA and expedite isolation of DNA segments linked to the disease.", "date": "1992", "date_type": "published", "publisher": "Elsevier", "place_of_pub": "New York, NY", "pagerange": "309-321", "id_number": "CaltechAUTHORS:20160510-145809040", "isbn": "978-0-12-182117-3", "book_title": "Recombinant DNA", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20160510-145809040", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH" }, { "agency": "Howard Hughes Medical Institute (HHMI)" } ] }, "doi": "10.1016/0076-6879(92)16029-J", "resource_type": "book_section", "pub_year": "1992", "author_list": "Strobel, S. A. and Dervan, P. B." }, { "id": "https://authors.library.caltech.edu/records/bd1c1-y0e33", "eprint_id": 66955, "eprint_status": "archive", "datestamp": "2023-08-19 23:30:39", "lastmod": "2024-01-13 16:50:49", "type": "book_section", "metadata_visibility": "show", "creators": { "items": [ { "id": "Dervan-P-B", "name": { "family": "Dervan", "given": "Peter B." }, "orcid": "0000-0001-8852-7306" } ] }, "title": "Characterization of protein-DNA complexes by affinity cleaving", "ispublished": "unpub", "full_text_status": "restricted", "note": "\u00a9 1991 Elsevier. \n\nThis work was supported by grants from the DARPA University Research Initiative Program and the National Foundation for Cancer Research. I am indebted to my students and coworkers who made this work possible; in particular, J. P. Sluka, D. P. Mack, J. H. Griffin, K. Graham, J. A. Shin, and M. G. Oakley. We are grateful for helpful discussions and collaborations with the M. J. Simon research group and for generous technical advice from S. B. H. Kent and S. J. Horvath.", "abstract": "High-resolution crystallographic views of protein-DNA complexes reveal the structural complexity of protein-DNA interactions. The combination of direct protein-DNA contacts mediated by multiple hydrogen bonds and sequence-dependent DNA conformational effects limits our\nability to make detailed structural predictions, even if a new DNA-binding protein can be assigned to a structural class such as helix-turn-helix, double-barreled helix, zinc-binding finger, or scissor grip-leucine zipper. \nIn the absence of high-resolution crystallographic and nuclear magnetic resonance (NMR) data, solution methods such as affinity cleaving can be used to characterize the topology of protein-DNA complexes and correlate\nsequence similarities with known structural classes.\n\nThe conversion of a sequence-specific DNA-binding protein into a sequence-specific DNA-cleaving protein by covalent attachment of the iron chelator, ethylenediaminetetraacetic acid (EDTA), to a specific amino acid residue creates a class of hybrid affinity-cleaving proteins that are\navailable through chemical synthesis. Moreover, a structural domain consisting of naturally occurring amino acids that binds transition metals and oxidatively cleaves DNA extends this method to recombinant methods\nfor protein synthesis.", "date": "1991", "date_type": "published", "publisher": "Academic Press", "place_of_pub": "San Diego, CA", "pagerange": "497-515", "id_number": "CaltechAUTHORS:20160510-145812699", "isbn": "978-0-12-182109-8", "book_title": "Protein 3- DNA Interactions", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20160510-145812699", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Defense Advanced Research Projects Agency (DARPA)" }, { "agency": "National Foundation for Cancer Research" } ] }, "doi": "10.1016/0076-6879(91)08026-E", "resource_type": "book_section", "pub_year": "1991", "author_list": "Dervan, Peter B." }, { "id": "https://authors.library.caltech.edu/records/pyngb-r2w39", "eprint_id": 67185, "eprint_status": "archive", "datestamp": "2023-08-19 22:15:56", "lastmod": "2023-10-18 20:55:47", "type": "book_section", "metadata_visibility": "show", "creators": { "items": [ { "id": "Dervan-P-B", "name": { "family": "Dervan", "given": "Peter B." }, "orcid": "0000-0001-8852-7306" } ] }, "title": "Chemical methods for the site-specific cleavage of genomic DNA", "ispublished": "unpub", "full_text_status": "restricted", "note": "\u00a9 1990 Adenine Press. \n\nWe thank the National Institutes of Health (GM-35724), the Office of Naval Research, the Parsons Foundation, Burroughs Wellcome, and Merck for generous financial support.", "abstract": "Pyrimidine oligodeoxyribonucleotides bind duplex DNA at homopurine sites to form a triple helix structure. The pyrimidine oligodeoxyribonucleotide is oriented in the major groove of DNA parallel to the Watson-Crick purine strand. Specificity is due to Hoogsteen hydrogen bonds wherein T recognizes A-T base pairs (T\u2022AT triplet) and protonated C recognizes GC base pairs (C + GC triplet). Oligonucleotides 18 bases in length, equipped with a DNA cleaving function EDTA\u2022Fe at the 5' end. cause sequence specific double strand breaks at one site in the 48.5 kbp bacteriophage \u03bb genome. Due to the length of the recognition site, in a formal sense. this is 10^6 times more sequence-specific that restriction enzymes. The triple helix motif can be extended from homopurine target sequences to mixed sequences. Oligonucleotide directed triple helix formation could be useful for mapping genomic DNA.", "date": "1990", "date_type": "published", "publisher": "Adenine Press", "pagerange": "37-49", "id_number": "CaltechAUTHORS:20160519-124144205", "isbn": "0-940030-29-2", "book_title": "Structure and Methods", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20160519-124144205", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "GM-35724" }, { "agency": "Office of Naval Research (ONR)" }, { "agency": "Ralph M. Parsons Foundation" }, { "agency": "Burroughs Wellcome" }, { "agency": "Merck" } ] }, "contributors": { "items": [ { "id": "Sarma-R-H", "name": { "family": "Sarma", "given": "Ramaswamy H." } }, { "id": "Sarma-M-H", "name": { "family": "Sarma", "given": "Mukti H." } } ] }, "resource_type": "book_section", "pub_year": "1990", "author_list": "Dervan, Peter B." }, { "id": "https://authors.library.caltech.edu/records/2c9bt-a8b46", "eprint_id": 67214, "eprint_status": "archive", "datestamp": "2023-08-19 22:16:04", "lastmod": "2023-10-18 20:57:52", "type": "book_section", "metadata_visibility": "show", "creators": { "items": [ { "id": "Breslauer-K-J", "name": { "family": "Breslauer", "given": "Kenneth J." } }, { "id": "Ferrante-R", "name": { "family": "Ferrante", "given": "Robert" } }, { "id": "Marky-L-A", "name": { "family": "Marky", "given": "Luis A." } }, { "id": "Dervan-P-B", "name": { "family": "Dervan", "given": "Peter B." }, "orcid": "0000-0001-8852-7306" }, { "id": "Youngquist-R-S", "name": { "family": "Youngquist", "given": "R. Scott" } } ] }, "title": "The Origins of the DNA Binding Affinity and Specificity of Minor Groove Directed Ligands: Correlations of Thermodynamic and Structural Data", "ispublished": "unpub", "full_text_status": "restricted", "note": "\u00a9 1990 Adenine Press. \n\nThis research was supported by grants GM23509 (KJB), GM34469 (KJB), and GM27681 (PBD).", "abstract": "We report complete thermodynamic binding profiles for the complexation of three minor groove directed ligands [netropsin. P2 (a synthetic analogue of netropsin), and distamycin A] to selected DNA host duplexes. From a comparison of the DNA binding profiles associated with these ligands, we are able to reach the following conclusions: \n1) The minor groove binding of each ligand is overwhelmingly enthalpy-driven and exhibits a very high binding affinity (K-109 at 25\u00b0C). \n2) The thermodynamic binding data primarily reflect local ligand-DNA interactions rather than long-range binding-induced conformational changes at regions distant from the binding site. \n3) Deep penetration into the minor groove is required to form those ligand-DNA interactions responsible for the enthalpy-driven high binding affinity. \n4) IC base pairs form min or groove binding sites for these ligands that thermodynamically are equivalent to those formed by AT base pairs. \n5) The enhanced binding affinity associated with deep penetration of the ligands into the minor groove does not result from more favorable electrostatic interactions. \n6) Removal of one of the two charged ends of a ligand (P2 versus netropsin) results in a reduction in binding affinity at 25\u00b0C that is entirely entropic in origin. \n7) The pyrrole/carboxamide bodies of these ligands rather than the charged-ends form the ligand interactions with the minor groove of DNA that give rise to the observed enthalpy driven high binding affinity. \n\nWe propose correlations between our thermodynamic data and specific molecular interactions defined by x-ray and NMR structural studies on similar and identical drug-DNA complexes. These correlations illustrate the power of parallel structural and thermodynamic studies for developing a microscopic understanding of macroscopic data.", "date": "1990", "date_type": "published", "publisher": "Adenine Press", "pagerange": "273-289", "id_number": "CaltechAUTHORS:20160520-133813535", "isbn": "0-940030-22-5", "book_title": "Structure and Methods", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20160520-133813535", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "GM-23509" }, { "agency": "NIH", "grant_number": "GM-34469" }, { "agency": "NIH", "grant_number": "GM-27681" } ] }, "contributors": { "items": [ { "id": "Sarma-R-H", "name": { "family": "Sarma", "given": "Ramaswamy H." } }, { "id": "Sarma-M-H", "name": { "family": "Sarma", "given": "Mukti H." } } ] }, "resource_type": "book_section", "pub_year": "1990", "author_list": "Breslauer, Kenneth J.; Ferrante, Robert; et el." }, { "id": "https://authors.library.caltech.edu/records/kpdwc-f3m65", "eprint_id": 67215, "eprint_status": "archive", "datestamp": "2023-08-19 21:12:06", "lastmod": "2024-01-13 16:51:30", "type": "book_section", "metadata_visibility": "show", "creators": { "items": [ { "id": "Griffin-J-H", "name": { "family": "Griffin", "given": "John H." } }, { "id": "Dervan-P-B", "name": { "family": "Dervan", "given": "Peter B." }, "orcid": "0000-0001-8852-7306" } ] }, "title": "Metalloregulation in the Sequence Specific Binding of Synthetic Molecules to DNA", "ispublished": "unpub", "full_text_status": "restricted", "note": "\u00a9 1989 Alan R. Liss. \n\nThis work was supported by NIH and by NSF and Merck Sharpe & Dohme/ACS fellowships to JHG.", "abstract": "The design, synthesis, and DNA binding studies of a series of bis(netropsin)s linked by homologous polyether tethers has been undertaken. DNA affinity cleaving experiments show that one compound, bis(netropsin)-3,6,9,12,15-pentaoxahepta-decanediamine-EDTA:Fe(II) (1b:Fe(II)) is positively activated for specific DNA binding in the presence of Sr^(2+) or Ba^(2+) ions. The effects of linker structure, metal ion concentration, and DNA sequence on the metalloregulated binding are reported.", "date": "1989", "date_type": "published", "publisher": "Alan R. Liss", "place_of_pub": "New York, NY", "pagerange": "21-30", "id_number": "CaltechAUTHORS:20160520-134443882", "isbn": "9780845126974", "book_title": "Metal ion homeostasis : molecular biology and chemistry", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20160520-134443882", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH" }, { "agency": "NSF" }, { "agency": "Merck Sharp & Dohme Research Laboratories" }, { "agency": "American Chemical Society" } ] }, "contributors": { "items": [ { "id": "Hamer-D-H", "name": { "family": "Hamer", "given": "Dean H." } }, { "id": "Winge-D-R", "name": { "family": "Winge", "given": "Dennis R." } } ] }, "resource_type": "book_section", "pub_year": "1989", "author_list": "Griffin, John H. and Dervan, Peter B." }, { "id": "https://authors.library.caltech.edu/records/aq64k-3kp63", "eprint_id": 67184, "eprint_status": "archive", "datestamp": "2023-08-19 21:11:59", "lastmod": "2024-01-13 16:51:25", "type": "book_section", "metadata_visibility": "show", "creators": { "items": [ { "id": "Dervan-P-B", "name": { "family": "Dervan", "given": "Peter B." }, "orcid": "0000-0001-8852-7306" } ] }, "title": "Oligonucleotide recognition of double-helical DNA by triple-helix formation", "ispublished": "unpub", "full_text_status": "restricted", "note": "\u00a9 1989 CRC Press. \n\nWe are grateful to the National Institutes of Health and the Office of Naval Research for generous grant support. In addition, unrestricted funds from Burroughs Wellcome, Merck, Hoffmann-La Roche and the Parsons Foundation are gratefully acknowledged.", "abstract": "The sequence-specific recognition of double-helical DNA is an essential biological process responsible for the regulation of cellular functions including transcription, replication and cell division. The ability to design synthetic molecules that bind sequence-specifically to unique sites on human DNA has major implications for the treatment of genetic, oncogenic and viral diseases. A detailed understanding of the chemical principles for binding specific sites on double-helical DNA with oligodeoxynucleotides (or their analogues) by triple-strand formation would provide a pivotal first step in the development of a novel chemotherapeutic strategy of genetic targeting. This could ultimately enable precise inactivation of undesirable DNA sequences within the human genome.", "date": "1989", "date_type": "published", "publisher": "CRC Press", "place_of_pub": "Boca Raton, FL", "pagerange": "197-210", "id_number": "CaltechAUTHORS:20160519-124134048", "isbn": "978-1-349-10871-8", "book_title": "Oligodeoxynucleotides: Antisense Inhibitors of Gene Expression", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20160519-124134048", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH" }, { "agency": "Office of Naval Research (ONR)" }, { "agency": "Burroughs-Wellcome" }, { "agency": "Merck" }, { "agency": "Hoffmann-La Roche" }, { "agency": "Ralph M. Parsons Foundation" } ] }, "contributors": { "items": [ { "id": "Cohen-J-S", "name": { "family": "Cohen", "given": "Jack S." } } ] }, "doi": "10.1007/978-1-349-10869-5_10", "resource_type": "book_section", "pub_year": "1989", "author_list": "Dervan, Peter B." }, { "id": "https://authors.library.caltech.edu/records/sjprd-kky80", "eprint_id": 67211, "eprint_status": "archive", "datestamp": "2023-08-19 20:08:31", "lastmod": "2023-10-18 20:57:40", "type": "book_section", "metadata_visibility": "show", "creators": { "items": [ { "id": "Dervan-P-B", "name": { "family": "Dervan", "given": "P. B." }, "orcid": "0000-0001-8852-7306" } ] }, "title": "Sequence Specific Recognition of Double Helical DNA. A Synthetic Approach", "ispublished": "unpub", "full_text_status": "restricted", "note": "\u00a9 1988 Springer. \n\nWe are grateful for the support of the National Institutes of Health, the American Cancer Society, DARPA, the National Foundation for Cancer Research, Merck, Burroughs-Wellcome, the Allied-Signal Corporation, and the Ralph M. Parsons Foundation.", "abstract": "The design of synthetic sequence-specific DNA-binding molecules has advanced in recent years due, in part, to analytical techniques such as foot-printing and affinity cleaving which allow rapid and precise analyses of hundreds of potential DNA-binding sites to nucleotide resolution on sequencing gels (Dervan 1986). During the past 10 years our group has focused on the construction of molecules that bind in the minor and major groove of DNA with incrementally increasing sequence specificity as a first step toward defining the chemical principles for creating specificity at the 15-base pair level (Dervan 1986). Recent progress illustrates how the tools of chemical synthesis in combination with nucleic acid techniques can be used to solve this problem. This may lead to new research tools useful in molecular biology, diagnosis of disease states at the level of DNA, and novel chemotherapeutic strategies such as artificial repressors for inactivation of these genes. The purpose of this chapter is not a comprehensive survey of the literature but rather a brief report of recent progress from our group using an experimental approach to the design of sequence-specific DNA-binding molecules.", "date": "1988", "date_type": "published", "publisher": "Springer-Verlag", "place_of_pub": "New York, NY", "pagerange": "49-64", "id_number": "CaltechAUTHORS:20160520-130010198", "isbn": "978-3-642-83386-1", "book_title": "Nucleic Acids and Molecular Biology", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20160520-130010198", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH" }, { "agency": "American Cancer Society" }, { "agency": "Defense Advanced Research Projects Agency (DARPA)" }, { "agency": "National Foundation for Cancer Research" }, { "agency": "Merck" }, { "agency": "Burroughs-Wellcome" }, { "agency": "Allied-Signal" }, { "agency": "Ralph M. Parsons Foundation" } ] }, "contributors": { "items": [ { "id": "Ekstein-F", "name": { "family": "Eckstein", "given": "Fritz" } }, { "id": "Lilley-D-M", "name": { "family": "Lilley", "given": "David M." } } ] }, "doi": "10.1007/978-3-642-83384-7_3", "resource_type": "book_section", "pub_year": "1988", "author_list": "Dervan, P. B." }, { "id": "https://authors.library.caltech.edu/records/qbfes-91r09", "eprint_id": 67183, "eprint_status": "archive", "datestamp": "2023-08-19 20:08:24", "lastmod": "2024-01-13 16:51:23", "type": "book_section", "metadata_visibility": "show", "creators": { "items": [ { "id": "Dervan-P-B", "name": { "family": "Dervan", "given": "Peter B." }, "orcid": "0000-0001-8852-7306" } ] }, "title": "Sequence specific recognition and cleavage of double helical DNA", "ispublished": "unpub", "full_text_status": "restricted", "note": "\u00a9 1988 Robert A. Welch Foundation. \n\nWe are grateful for the support of the National Institutes of Health, the American Cancer Society, DAPRA, Burroughs-Wellcome, the Allied-Signal Corporation, the Smith Kline Beckman Corporation and the Ralph M. Parsons Foundation.", "abstract": "Deoxyribonucleic acid (DNA) is the stuff of our genes. There are four bases (A, T, G, C) possible for each nucleotide position on each strand of the DNA double helix. Human DNA consists of 3 x 10^9 base pairs. Within these molecules contains the information; what makes humans grow, what makes humans different, and what makes humans human. Within the constraints of the A,T and G,C complementary nature of double helical DNA, for a binding site size of n base pairs there are (4^n)/2 distinguishable sequences for odd n, and (4^n)/2 + (4^(n/2))/2 for even n. Ten years ago we embarked on a program to understand the chemical principles that would make possible the sequence specific recognition of DNA uniquely at the chromosome level (one site in 10^8 base pairs). This requires specific recognition at the \u2265 15 base pair level. \n\nIn order to analyze the large numbers of potential binding sites on DNA for synthetic sequence specific DNA binding molecules, we realized that the construction of molecules with two separate structural and functional domains: sequence specific recognition and non-specific cleavage of DNA would allow the powerful methods for separating DNA fragments such as gel electrophoresis to be brought to bear on the DNA recognition analysis. Indeed, the design of synthetic sequence specific DNA binding molecules has advanced in recent years due to analytical techniques such as footprinting and affinity cleaving which allow rapid and precise analyses of hundreds of potential DNA binding sites to nucleotide resolution on sequencing gels (Dervan, 1986). Our group has focused on the construction of molecules that bind in the minor and major groove of DNA with incrementally increasing sequence specificity as a first step toward defining the chemical principles for creating specificity at the \u2265 15 base pair level (Dervan, 1986). The tools of chemical synthesis are used in combination with nucleic acid techniques. This may lead to new reagents for mapping chromosomes, diagnosis of disease states at the level of DNA, and novel chemotherapeutic strategies such as artificial repressors for inactivation of these genes. This lecture is a brief report on progress in design of sequence specific DNA binding molecules.", "date": "1988", "date_type": "published", "publisher": "Robert A. Welch Foundation", "id_number": "CaltechAUTHORS:20160519-124122958", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20160519-124122958", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH" }, { "agency": "American Cancer Society" }, { "agency": "Defense Advanced Research Projects Agency (DARPA)" }, { "agency": "Burroughs-Wellcome" }, { "agency": "Allied-Signal" }, { "agency": "Smith Kline Beckman" }, { "agency": "Ralph M. Parsons Foundation" } ] }, "resource_type": "book_section", "pub_year": "1988", "author_list": "Dervan, Peter B." }, { "id": "https://authors.library.caltech.edu/records/pkty3-zkv39", "eprint_id": 67212, "eprint_status": "archive", "datestamp": "2023-08-19 20:08:36", "lastmod": "2023-10-18 20:57:43", "type": "book_section", "metadata_visibility": "show", "creators": { "items": [ { "id": "Dervan-P-B", "name": { "family": "Dervan", "given": "Peter B." }, "orcid": "0000-0001-8852-7306" } ] }, "title": "Synthetic Tools for Molecular Biology", "ispublished": "unpub", "full_text_status": "public", "note": "\u00a9 1988 American Chemical Society. \n\nThe author is grateful to the National Institutes of Health, the American Cancer Society, the DARPA University Initiative Research Program, Allied Signal Corporation, Merck Sharp & Dohme, Research Laboratories, Burroughs-Wellcome Company and the Ralph M. Parsons Foundation for generous support. In addition, stimulating and helpful discussions with Dr. Ralph Hisrchmann are gratefully acknowledged.\n\n
Published - 73.pdf
", "abstract": "Chemistry has made tremendous advances over the past four decades in the broad fields of synthesis and understanding chemical reactivity. In that same time span, a series of revolutionary events occurred in biology. First came the discovery of the double helical structure of DNA in the 1950s by Watson and Crick. This discovery allowed the elucidation of the mechanisms of DNA replication -- how DNA makes copies of itself -- and DNA transcription and translation -- the processes that allow the genetic code to be read and translated into proteins. In the 1970s, the techniques that permit DNA to be cut and spliced in controlled and well-defined ways were invented and the technology of recombinant DNA was born.", "date": "1988", "date_type": "published", "publisher": "American Chemical Society", "place_of_pub": "Washington, DC", "pagerange": "21-29", "id_number": "CaltechAUTHORS:20160520-130857609", "isbn": "9780841214736", "book_title": "Biotechnology and materials science : chemistry for the future", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20160520-130857609", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH" }, { "agency": "American Cancer Society" }, { "agency": "Defense Advanced Research Projects Agency (DARPA)" }, { "agency": "Allied Signal" }, { "agency": "Merck Sharp & Dohme Research Laboratories" }, { "agency": "Burroughs-Wellcome" }, { "agency": "Ralph M. Parsons Foundation" } ] }, "contributors": { "items": [ { "id": "Good-M-L", "name": { "family": "Good", "given": "Mary L." } } ] }, "primary_object": { "basename": "73.pdf", "url": "https://authors.library.caltech.edu/records/pkty3-zkv39/files/73.pdf" }, "resource_type": "book_section", "pub_year": "1988", "author_list": "Dervan, Peter B." }, { "id": "https://authors.library.caltech.edu/records/p57te-knm64", "eprint_id": 67182, "eprint_status": "archive", "datestamp": "2023-08-19 19:10:01", "lastmod": "2024-01-13 16:51:21", "type": "book_section", "metadata_visibility": "show", "creators": { "items": [ { "id": "Dervan-P-B", "name": { "family": "Dervan", "given": "Peter B." }, "orcid": "0000-0001-8852-7306" } ] }, "title": "Design of synthetic sequence specific DNA binding molecules", "ispublished": "unpub", "full_text_status": "public", "note": "\u00a9 1987 Pontificiae Academiae Scientiarum. \n\nWe are very grateful for the generous support of the National Institutes of Health, the American Cancer Society, the National Foundation for Cancer Research, the Burroughs-Wellcome Company, and the Smith Kline Beckman Corporation.\n\nPublished - 60.pdf
", "abstract": "The design of sequence specific DNA binding molecules has advanced in recent years due, in part, to analytical techniques such as footprinting and affinity cleaving which allow rapid and precise analysis of hundreds of potential DNA binding sites on sequencing gels (Dervan, 1986 ). Nona-N-methylpyrrolecarboxamide, a synthetic analog of the natural product distamycin, binds 11 contiguous base pairs of A,T rich DNA in the minor groove. A synthetic polypeptide, 52 amino acid residues in length and derived from a recombinase protein, binds uniquely 12 base pairs of DNA, most likely in the major and minor groove. The construction of synthetic molecules that bind in the minor and major groove of DNA with incrementally increasing sequence specificity is the first step toward defining a set of rules for the three-dimensional readout of double helical DNA. This may lead to new research tools for use in cancer research, diagnosis of disease states at the level of DNA (oncogenes), and novel chemotherapeutic strategies such as artificial repressors for inactivation of these genes.", "date": "1987", "date_type": "published", "publisher": "Pontificiae Academiae Scientiarum", "place_of_pub": "Vatican City", "pagerange": "365-384", "id_number": "CaltechAUTHORS:20160519-124109662", "isbn": "9788877610232", "book_title": "Working Group on Molecular Mechanisms of Carcinogenic and Antitumor Activity, October 21-25, 1986", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20160519-124109662", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH" }, { "agency": "American Cancer Society" }, { "agency": "National Foundation for Cancer Research" }, { "agency": "Burroughs-Wellcome" }, { "agency": "Smith Kline Beckman" } ] }, "contributors": { "items": [ { "id": "Chagas-Filho-C", "name": { "family": "Chagas Filho", "given": "Carlos" } } ] }, "primary_object": { "basename": "60.pdf", "url": "https://authors.library.caltech.edu/records/p57te-knm64/files/60.pdf" }, "resource_type": "book_section", "pub_year": "1987", "author_list": "Dervan, Peter B." }, { "id": "https://authors.library.caltech.edu/records/y3xwr-wa723", "eprint_id": 67189, "eprint_status": "archive", "datestamp": "2023-08-19 19:10:08", "lastmod": "2023-10-18 20:56:09", "type": "book_section", "metadata_visibility": "show", "creators": { "items": [ { "id": "Dervan-P-B", "name": { "family": "Dervan", "given": "Peter B." }, "orcid": "0000-0001-8852-7306" }, { "id": "Youngquist-R-S", "name": { "family": "Youngquist", "given": "R. Scott" } }, { "id": "Sluka-J-P", "name": { "family": "Sluka", "given": "James P." } } ] }, "title": "Synthetic sequence specific DNA binding molecules", "ispublished": "unpub", "full_text_status": "restricted", "note": "\u00a9 1987 VCH. \n\nWe are very grateful for the generous support of the National Institutes of Health, the American Cancer Society, the National Foundation for Cancer Research, the DARPA University Research Initiative Program, Burroughs-Wellcome Company, the Allied-Signal Corporation and the Smith Kline Beckman Corporation.", "abstract": "The design of sequence specific DNA-binding molecules has advanced in recent years due, in part, to the development of analytical techniques such as footprinting and affinity cleaving which allow rapid and precise analysis of hundreds of of potential DNA binding sites. The construction of synthetic molecules that bind in the minor and major groove of DNA with incrementally increasing sequence specificity is simply the first step toward developing a set of rules for the three-dimensional readout of double helical DNA.", "date": "1987", "date_type": "published", "publisher": "VCH", "place_of_pub": "New York, NY", "pagerange": "221-234", "id_number": "CaltechAUTHORS:20160519-124245836", "isbn": "0895736071", "book_title": "Stereochemistry of organic and bioorganic transformations", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20160519-124245836", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH" }, { "agency": "American Cancer Society" }, { "agency": "National Foundation for Cancer Research" }, { "agency": "Defense Advanced Research Projects Agency (DARPA)" }, { "agency": "Burroughs-Wellcome" }, { "agency": "Allied-Signal" }, { "agency": "Smith Kline Beckman" } ] }, "contributors": { "items": [ { "id": "Bartmann-W", "name": { "family": "Bartmann", "given": "Wilhelm" } }, { "id": "Sharpless-K-B", "name": { "family": "Sharpless", "given": "K. Barry" } } ] }, "resource_type": "book_section", "pub_year": "1987", "author_list": "Dervan, Peter B.; Youngquist, R. Scott; et el." }, { "id": "https://authors.library.caltech.edu/records/k8aj7-2rw51", "eprint_id": 67187, "eprint_status": "archive", "datestamp": "2023-08-19 18:15:57", "lastmod": "2024-01-13 16:51:26", "type": "book_section", "metadata_visibility": "show", "creators": { "items": [ { "id": "Dervan-P-B", "name": { "family": "Dervan", "given": "P. B." }, "orcid": "0000-0001-8852-7306" }, { "id": "Sluka-J-P", "name": { "family": "Sluka", "given": "J. P." } } ] }, "title": "Design of sequence specific DNA binding molecules: bis(distamycin)phenoxazone", "ispublished": "unpub", "full_text_status": "restricted", "note": "\u00a9 1986 Elsevier. \n\nWe are grateful for generous support from the National Institutes of Health (GM-27681) and the National Foundation for Cancer Research.", "abstract": "One approach to the design of sequence specific DNA binding molecules that read large sequences of right-handed double helical DNA is to couple DNA binding units of similar or diverse base pair specificities. The natural product distamycin is a tris-N-methylpyrrolecaboxamide tripetide that binds in the minor groove of DNA at A\u2022T rich sequences that are five base pairs in size. The natural product actinomycin D which consists of an aromatic phenoxazone coupled to two identical pentapeptide lactones is an intercalator which binds four base pairs with a preference for 5'-NGCN-3' sequences. The synthesis of a hybrid distamycin and actinomycin, bis(distamycin)phenoxazone is described where the cyclic pentapeptides of actinomycin are replaced by the tripeptide of distamycin. Using the affinity cleaving method we find that bis(EDTA-distamycin)phenoxazone (BEDP) binds the sequence 5'-TATAGGTTAA-3' consistent with simultaneous binding of the tripeptides flanking the intercalator. At other sites the results indicate that the tripeptides do not bind simultaneously. One interpretation of the data suggests that the distortion of the DNA sequences flanking the phenoxazone intercalation site may be sequence specific and thus prevent binding of both tripeptide groover binders.", "date": "1986", "date_type": "published", "publisher": "Elsevier", "place_of_pub": "New York, NY", "pagerange": "307-322", "id_number": "CaltechAUTHORS:20160519-124217666", "isbn": "9780444989963", "book_title": "New Synthetic Methodology and Functionally Interesting Compounds", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20160519-124217666", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "GM-27681" }, { "agency": "National Foundation for Cancer Research" } ] }, "contributors": { "items": [ { "id": "Yoshida-Zen-ichi", "name": { "family": "Yoshida", "given": "Zen-ichi" } } ] }, "resource_type": "book_section", "pub_year": "1986", "author_list": "Dervan, P. B. and Sluka, J. P." }, { "id": "https://authors.library.caltech.edu/records/4p7j8-4mb63", "eprint_id": 67210, "eprint_status": "archive", "datestamp": "2023-08-19 14:44:00", "lastmod": "2023-10-18 20:57:35", "type": "book_section", "metadata_visibility": "show", "creators": { "items": [ { "id": "Dervan-P-B", "name": { "family": "Dervan", "given": "Peter B." }, "orcid": "0000-0001-8852-7306" }, { "id": "Dougherty-D-A", "name": { "family": "Dougherty", "given": "Dennis A." }, "orcid": "0000-0003-1464-2461" } ] }, "title": "Nonconjugated Diradicals", "ispublished": "unpub", "full_text_status": "restricted", "note": "\u00a9 1982 John Wiley & Sons.", "abstract": "Few reactions are as conceptually simple as the stretching of a carbon-carbon bond in a carbocyclic ring to afford a bond-broken species, a diradical (1-11). The list of thermal and photochemical reactions that appear to involve diradical structures as intermediates is long, much longer than the handful documented to proceed by concerted processes (12). To use the diradical hypothesis as a predictive tool, it is necessary to define a set of properties for diradicals. However, because most nonconjugated diradicals are short-lived, few direct data on their behavior exist. To date most studies on the properties of diradicals have been confined to indirect methods. \n\nIn this chapter, rather than present a compendium of all thermal and photochemical reactions thought to involve nonconjugated diradical pathways, we review the literature selectively to find general features of diradical behavior. Specific questions we address are: (a) What are the relative rates of the reaction of diradicals? (b) Is there evidence for diradicals as common intermediates? (c) What is the influence on diradical behavior of variables such as method of generation, substitution, temperature, and spin state? (d) What are the magnitude and consequences of interactions between the radical centers? (e) What are the lifetimes of diradicals? \n\nThe most-studied nonconjugated diradicals are the 1,3- and 1,4-diradicals. It may seem logical to start with the smaller 1,3-diradical where the radical centers are \"insulated\" by only one methylene unit. However, the trimelthylene story is complex, perhaps because the radical centers may interact significantly. In contrast, tetramethlyene seems to be more well behaved with regard to our chemical intuition of a \"classical\" diradical. For this reason, we review the 1,4-diradical first as a model of conventional diradical behavior and then proceed to the more complicated 1,3-system.", "date": "1982", "date_type": "published", "publisher": "John Wiley & Sons", "place_of_pub": "New York, NY", "pagerange": "107-149", "id_number": "CaltechAUTHORS:20160520-123957201", "isbn": "0471086614", "book_title": "Diradicals", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20160520-123957201", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "contributors": { "items": [ { "id": "Borden-W-T", "name": { "family": "Borden", "given": "Weston Thatcher" } } ] }, "resource_type": "book_section", "pub_year": "1982", "author_list": "Dervan, Peter B. and Dougherty, Dennis A." } ]