{"doi":"10.1038/nchembio.2520","title":"Inhibition of Delta-induced Notch signaling using fucose analogs","abstract":null,"journal":"Nature Chemical Biology","year":2018,"id":672518,"datarank":0.6064576901751826,"base_score":4.04305126783455,"endowment":4.04305126783455,"self_citation_contribution":0.6064576901751826,"citation_network_contribution":0.0,"self_endowment_contribution":0.6064576901751826,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":56,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":315580,"name":"Vivek Kumar","orcid":"0000-0001-7536-9281","position":1,"is_corresponding":false},{"id":747747,"name":"Lars Ulrik Nordstrøm","orcid":null,"position":2,"is_corresponding":false},{"id":362367,"name":"Lei Feng","orcid":"0000-0001-7687-2209","position":3,"is_corresponding":false},{"id":467284,"name":"Hideyuki Takeuchi","orcid":"0000-0002-2362-5850","position":4,"is_corresponding":false},{"id":468476,"name":"Huilin Hao","orcid":null,"position":5,"is_corresponding":false},{"id":1757101,"name":"Vincent C Luca","orcid":null,"position":6,"is_corresponding":false},{"id":1626043,"name":"K Christopher Garcia","orcid":null,"position":7,"is_corresponding":false},{"id":362372,"name":"Pamela Stanley","orcid":"0000-0001-5704-3747","position":8,"is_corresponding":false},{"id":262641,"name":"Peng Wu","orcid":"0000-0002-5204-0229","position":9,"is_corresponding":false},{"id":1757102,"name":"Robert S Haltiwanger","orcid":null,"position":10,"is_corresponding":false},{"id":659013,"name":"Michael Schneider","orcid":"0000-0002-6491-8852","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Inhibition of Delta-induced Notch signaling using fucose analogs","abstract":"Notch is a cell-surface receptor that controls cell-fate decisions and is regulated by O-glycans attached to epidermal growth factor-like (EGF) repeats in its extracellular domain. Protein O-fucosyltransferase 1 (Pofut1) modifies EGF repeats with O-fucose and is essential for Notch signaling. Constitutive activation of Notch signaling has been associated with a variety of human malignancies. Therefore, tools that inhibit Notch activity are being developed as cancer therapeutics. To this end, we screened L-fucose analogs for their effects on Notch signaling. Two analogs, 6-alkynyl and 6-alkenyl fucose, were substrates of Pofut1 and were incorporated directly into Notch EGF repeats in cells. Both analogs were potent inhibitors of binding to and activation of Notch1 by Notch ligands Dll1 and Dll4, but not by Jag1. Mutagenesis and modeling studies suggest that incorporation of the analogs into EGF8 of Notch1 markedly reduces the ability of Delta ligands to bind and activate Notch1.","is_dataset_classified":null,"base_score":4.04305126783455,"endowment":4.04305126783455,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"29176671","pmcid":"PMC5726916","openalex_id":"https://openalex.org/W2769185894","authors":[],"funders":[{"funder_name":"NIGMS NIH HHS","grant_id":"R01 GM061126","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"T32 GM008444","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"P30 DK041296","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"R01 GM093282","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"R01 GM106417","title":null},{"funder_name":"NCI NIH HHS","grant_id":"K99 CA204738","title":null},{"funder_name":"National Institutes of Health","grant_id":"9R01GM106417-11A1","title":"Roles of Glycoslyation in Notch Signaling"},{"funder_name":"National Institutes of Health","grant_id":"3K99CA204738-01S1","title":"Deconstructing the molecular mechanisms of Notch receptor-ligand selectivity"},{"funder_name":"National Institutes of Health","grant_id":"2R01GM061126-09","title":"O-Glycosylation of Epidermal Growth Factor-like Modules"},{"funder_name":"National Institutes of Health","grant_id":"6R01GM093282-06","title":"Chemical tools for studying fucosylated glycans"}],"total_grants":10,"fwci":2.8376,"citation_percentile":0.91844557,"influential_citations":0,"citation_trend":[{"year":2017,"count":2},{"year":2018,"count":5},{"year":2019,"count":10},{"year":2020,"count":11},{"year":2021,"count":6},{"year":2022,"count":6},{"year":2023,"count":6},{"year":2024,"count":2},{"year":2025,"count":6},{"year":2026,"count":2}],"oa_status":"green","license":"Springer TDM","oa_locations":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/5726916","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/5726916","host_type":"repository"},{"url":"http://www.nature.com/articles/nchembio.2520.pdf","host_type":"publisher"},{"url":"http://www.nature.com/articles/nchembio.2520","host_type":"publisher"},{"url":"http://www.nature.com/doifinder/10.1038/nchembio.2520","host_type":"publisher"},{"url":"https://doi.org/10.1038/nchembio.2520","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/29176671","host_type":"repository"},{"url":"http://europepmc.org/pmc/articles/PMC5726916","host_type":"repository"},{"url":"https://commons.library.stonybrook.edu/stony-brook-theses-and-dissertations-collection/3859","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC5726916","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC5726916?pdf=render","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/pmc5726916?pdf=render","host_type":""},{"url":"http://dx.doi.org/10.1038/nchembio.2520","host_type":""},{"url":"https://dx.doi.org/10.1038/nchembio.2520","host_type":""}],"fields_of_study":["Developmental Biology and Gene Regulation","Marine Sponges and Natural Products","Invertebrate Immune Response Mechanisms","0301 basic medicine","03 medical and health sciences","Animals","EGF Family of Proteins","Fucose","Fucosyltransferases","HEK293 Cells","Humans","Intracellular Signaling Peptides and Proteins","Ligands","Membrane Proteins","Protein Binding","Receptors, Notch","Signal Transduction"],"mesh_terms":["Animals","Fucose","Fucosyltransferases","Humans","Ligands","Membrane Proteins","Protein Binding","Signal Transduction","Intracellular Signaling Peptides and Proteins","Receptors, Notch","HEK293 Cells","EGF Family of Proteins"],"keywords":["Notch signaling pathway","Notch proteins","EGF-like domain","Cell biology","Fucose","Cyclin-dependent kinase 8","JAG1","Epidermal growth factor","Hes3 signaling axis","Signal transduction","Biology","Extracellular","Chemistry","Biochemistry","Receptor","Binding domain","Binding site","Glycoprotein","EGF Family of Proteins","Receptors, Notch","Intracellular Signaling Peptides and Proteins","Membrane Proteins","Fucosyltransferases","Ligands","Article","HEK293 Cells","Animals","Humans","Protein Binding"],"sdg_mappings":[{"sdg_number":3,"sdg_label":"3. 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