title: Highly diverse heparan sulfate analogue libraries: providing access to expanded areas of sequence space for bioactivity screening.
abstract: Structurally diverse heparan sulfate analogue libraries were produced chemicoenzymatically from heparin. They possess vastly more heterogeneity than tissue heparan sulfates, expand the sequence space available for screening, and can help identify minimal structural features associated with activity. Library components are likely to exhibit fewer nonspecific interactions and side-effects than heparin or simple chemically modified heparin. A strategy for their use is illustrated for the fibroblast growth factor-receptor tyrosine kinase signaling system.
authors.affiliation: School of Biosciences, University of Birmingham, Birmingham, B15 2TT, U.K. ed_yates@hotmail.com
authors.forename: Edwin A
authors.initials: EA
authors.lastname: Yates
authors.forename: Scott E
authors.initials: SE
authors.lastname: Guimond
authors.forename: Jeremy E
authors.initials: JE
authors.lastname: Turnbull
mesh_terms: D002460:Cell Line; D020650:Combinatorial Chemistry Techniques; D016208:Databases, Factual; D004798:Enzymes / Q000737:chemistry; D016220:Fibroblast Growth Factor 1 / Q000502:physiology; D006493:Heparin / Q000737:chemistry; D006497:Heparan Sulfate / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry*; D009844:Oligosaccharides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D020794:Receptor Protein-Tyrosine Kinases / Q000502:physiology; D051497:Receptor, Fibroblast Growth Factor, Type 2; D017468:Receptors, Fibroblast Growth Factor / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D004798:Enzymes; D016220:Fibroblast Growth Factor 1; D006493:Heparin; D006497:Heparan Sulfate; D009844:Oligosaccharides; D020794:Receptor Protein-Tyrosine Kinases; D051497:Receptor, Fibroblast Growth Factor, Type 2; D017468:Receptors, Fibroblast Growth Factor