title: Synthesis and characterization of photoaffinity labelling reagents towards the Hsp90 C-terminal domain.
abstract: Glucosyl-novobiocin-based diazirine photoaffinity labelling reagents (PALs) were designed and synthesized to probe the Hsp90 C-terminal domain unknown binding pocket and the structure-activity relationship. Five PALs were successfully synthesized from novobiocin in six consecutive steps employing phase transfer catalytic glycosylation. Reactions were monitored and guided by analytical LC/MS which led to different strategies of adding either a PAL precursor or a sugar moiety first. The structures and bonding linkages of these compounds were characterised by various 2D-NMR spectroscopy and MS techniques. Synthetic techniques provide powerful probes for unknown protein binding pockets.
authors.affiliation: Department of Pharmaceutical & Biological Chemistry, The School of Pharmacy, University College London, London WC1N 1AX, UK. min.yang@ucl.ac.uk.
authors.forename: Binto
authors.initials: B
authors.lastname: Simon
authors.forename: Xuexia
authors.initials: X
authors.lastname: Huang
authors.forename: Huangxian
authors.initials: H
authors.lastname: Ju
authors.forename: Guoxuan
authors.initials: G
authors.lastname: Sun
authors.forename: Min
authors.initials: M
authors.lastname: Yang
mesh_terms: D018841:HSP90 Heat-Shock Proteins / Q000737:chemistry*; D007202:Indicators and Reagents / Q000138:chemical synthesis* / Q000737:chemistry*; D015394:Molecular Structure; D019920:Photoaffinity Labels / Q000138:chemical synthesis* / Q000737:chemistry*
chemical_list: D018841:HSP90 Heat-Shock Proteins; D007202:Indicators and Reagents; D019920:Photoaffinity Labels