[ { "id": "authors:00d8n-1k538", "collection": "authors", "collection_id": "00d8n-1k538", "cite_using_url": "https://authors.library.caltech.edu/records/00d8n-1k538", "type": "monograph", "title": "Functional glycoproteomics by integrated network assembly and partitioning", "author": [ { "family_name": "Griffin", "given_name": "Matthew E.", "orcid": "0000-0001-9549-4418", "clpid": "Griffin-Matthew-E" }, { "family_name": "Thompson", "given_name": "John W.", "orcid": "0000-0003-0061-4996", "clpid": "Thompson-John-W" }, { "family_name": "Xiao", "given_name": "Yao", "orcid": "0009-0002-4420-7153", "clpid": "Xiao-Yao" }, { "family_name": "Sweredoski", "given_name": "Michael J.", "orcid": "0000-0003-0878-3831", "clpid": "Sweredoski-Michael-J" }, { "family_name": "Aksenfeld", "given_name": "Rita B.", "orcid": "0000-0002-2911-9211", "clpid": "Aksenfeld-Rita-B" }, { "family_name": "Jensen", "given_name": "Elizabeth H.", "clpid": "Jensen-Elizabeth-H" }, { "family_name": "Koldobskaya", "given_name": "Yelena", "clpid": "Koldobskaya-Yelena" }, { "family_name": "Schacht", "given_name": "Andrew L.", "orcid": "0000-0002-7998-393X", "clpid": "Schacht-Andrew-L" }, { "family_name": "Kim", "given_name": "Terry D.", "orcid": "0000-0001-7259-5486", "clpid": "Kim-Terry-D" }, { "family_name": "Choudhry", "given_name": "Priya", "orcid": "0000-0002-4438-1576", "clpid": "Choudhry-Priya" }, { "family_name": "Lomenick", "given_name": "Brett", "orcid": "0000-0002-5023-9998", "clpid": "Lomenick-Brett" }, { "family_name": "Garbis", "given_name": "Spiros D.", "orcid": "0000-0002-1050-0805", "clpid": "Garbis-Spiros-D" }, { "family_name": "Moradian", "given_name": "Annie", "orcid": "0000-0002-0407-2031", "clpid": "Moradian-Annie" }, { "family_name": "Hsieh-Wilson", "given_name": "Linda C.", "orcid": "0000-0001-5661-1714", "clpid": "Hsieh-Wilson-L-C" } ], "abstract": "
\n

The post-translational modification (PTM) of proteins by O-linked β-N-acetyl-D-glucosamine (O-GlcNAcylation) is widespread across the proteome during the lifespan of all multicellular organisms. However, nearly all functional studies have focused on individual protein modifications, overlooking the multitude of simultaneous O-GlcNAcylation events that work together to coordinate cellular activities. Here, we describe Networking of Interactors and SubstratEs (NISE), a novel, systems-level approach to rapidly and comprehensively monitor O-GlcNAcylation across the proteome. Our method integrates affinity purification-mass spectrometry (AP-MS) and site-specific chemoproteomic technologies with network generation and unsupervised partitioning to connect potential upstream regulators with downstream targets of O-GlcNAcylation. The resulting network provides a data-rich framework that reveals both conserved activities of O-GlcNAcylation such as epigenetic regulation as well as tissue-specific functions like synaptic morphology. Beyond O-GlcNAc, this holistic and unbiased systems-level approach provides a broadly applicable framework to study PTMs and discover their diverse roles in specific cell types and biological states.

\n
", "doi": "10.1101/2023.06.13.541482", "pmcid": "PMC10312638", "publisher": "Cold Spring Harbor Laboratory Press", "publication_date": "2023-06-14" }, { "id": "authors:eg8fb-d8063", "collection": "authors", "collection_id": "eg8fb-d8063", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20230324-457118000.6", "type": "monograph", "title": "Automated Platform for the Synthesis of Heparan Sulfate Oligosaccharide Libraries for Decoding Glycosaminoglycan-Protein Interactions", "author": [ { "family_name": "Wang", "given_name": "Lei", "orcid": "0000-0002-1087-8437", "clpid": "Wang-Lei" }, { "family_name": "Huang", "given_name": "Bo-Shun", "orcid": "0000-0003-2394-0292", "clpid": "Huang-Bo-Shun" }, { "family_name": "Sorum", "given_name": "Alexander W.", "orcid": "0000-0003-2526-1445", "clpid": "Sorum-Alexander-W" }, { "family_name": "Kern", "given_name": "Mallory", "orcid": "0000-0003-4878-4636", "clpid": "Kem-Mallory" }, { "family_name": "Su", "given_name": "Guowei", "orcid": "0000-0003-2668-9275", "clpid": "Su-Guowei" }, { "family_name": "Huang", "given_name": "Xuefei", "orcid": "0000-0002-6468-5526", "clpid": "Huang-Xuefei" }, { "family_name": "Liu", "given_name": "Jian", "orcid": "0000-0001-8552-1400", "clpid": "Liu-Jian" }, { "family_name": "Pohl", "given_name": "Nicola L. B.", "orcid": "0000-0001-7747-8983", "clpid": "Pohl-Nicola-L-B" }, { "family_name": "Hsieh-Wilson", "given_name": "Linda C.", "orcid": "0000-0001-5661-1714", "clpid": "Hsieh-Wilson-L-C" } ], "abstract": "Glycosaminoglycans (GAGs) are abundant, ubiquitous carbohydrates in biology, yet their structural complexity has limited an understanding of their biological roles and structure-function relationships. Synthetic access to large collections of well-defined, structurally diverse GAG oligosaccharides would provide critical insights into this important class of biomolecules and represent a major advance in glycoscience. Here, we report a new automated platform for synthesizing heparan sulfate (HS) oligosaccharide libraries displaying comprehensive arrays of sulfation patterns. Library synthesis is made possible by improving the overall synthetic efficiency through universal building blocks derived from natural heparin and a traceless fluorous tagging method for rapid purification and automated synthesis. We used this approach to generate the first comprehensive library of 64 HS tetrasaccharides displaying all possible 2-O-, 6-O-, and N-sulfation sequences. These diverse structures provide an unprecedented view into the sulfation code of GAGs and identify sequences for modulating the activities of important growth factors and chemokines.", "doi": "10.26434/chemrxiv-2022-79tzx", "publication_date": "2022-10-03" }, { "id": "authors:tr3f7-a3x09", "collection": "authors", "collection_id": "tr3f7-a3x09", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20220711-653217000", "type": "monograph", "title": "Expedient Synthesis of a Library of Heparan Sulfate Like \"Head to Tail\" Linked Multimers for Structure and Activity Relationship Studies", "author": [ { "family_name": "Zhang", "given_name": "Jicheng", "clpid": "Zhang-Jicheng" }, { "family_name": "Liang", "given_name": "Li", "clpid": "Liangf-Li" }, { "family_name": "Yang", "given_name": "Weizhun", "orcid": "0000-0001-5522-4026", "clpid": "Yang-Weizhun" }, { "family_name": "Ramadan", "given_name": "Sherif", "orcid": "0000-0002-8639-4105", "clpid": "Ramadan-Sherif" }, { "family_name": "Baryal", "given_name": "Kedar", "orcid": "0000-0003-1840-7485", "clpid": "Baryal-Kedar" }, { "family_name": "Huo", "given_name": "Chang-Xin", "clpid": "Huo-Chang-Xin" }, { "family_name": "Bernard", "given_name": "Jamie J.", "orcid": "0000-0002-3800-2576", "clpid": "Bernard-Jamie-J" }, { "family_name": "Liu", "given_name": "Jian", "orcid": "0000-0001-8552-1400", "clpid": "Liu-Jian" }, { "family_name": "Hsieh-Wilson", "given_name": "Linda", "orcid": "0000-0001-5661-1714", "clpid": "Hsieh-Wilson-L-C" }, { "family_name": "Zhang", "given_name": "Fuming", "clpid": "Zhang-Fuming" }, { "family_name": "Linhardt", "given_name": "Robert J.", "orcid": "0000-0003-2219-5833", "clpid": "Linhardt-Robert-J" }, { "family_name": "Huang", "given_name": "Xuefei", "orcid": "0000-0002-6468-5526", "clpid": "Huang-Xuefei" } ], "abstract": "Heparan sulfate (HS) plays significant roles in various biological processes such as inflammation, cell proliferation, and bacterial and viral infection. The inherent complexity of naturally existing HS has severely hindered the thorough understanding of the relationship between their diverse structures and biological functions. While HS syntheses have advanced significantly in recent years, preparation of HS libraries remains a tremendous challenge due to the difficulties in achieving high yields in glycosylation and sulfation reactions especially with longer glycans and the need to prepare multiple compounds. A new strategy to synthesize a library of HS-like pseudo-hexasaccharides has been developed to expedite library preparation. HS disaccharides were linked in a \"head-to-tail\" fashion from the reducing end of a module to the non-reducing end of a neighboring module to mimic native HS. Three differentially sulfated HS disaccharides were designed and prepared from a common intermediate. Conjugation of these modules using amide chemistry bypassed the need for challenging glycosylation reactions to extend the HS backbone. Combinatorial syntheses of 27 HS-like pseudo-hexasaccharides were achieved using these three HS modules. This new class of compounds mimicked well the native HS with their binding to fibroblast growth factor 2 (FGF-2) exhibiting similar structure-activity relationship trends as HS hexasaccharides. The ease of synthesis and the ability to mimic natural HS suggest the new head-to-tail linked pseudo-hexasaccharides could be an exciting tool to facilitate the understanding of HS biology.", "doi": "10.26434/chemrxiv-2022-m03tb-v2", "publication_date": "2022-07-01" } ]