title: Synthesis and evaluation of biotinylated sansalvamide A analogs and their modulation of Hsp90.
abstract: Described are the syntheses of three sansalvamide A derivatives that contain biotinylated tags at individual positions around the macrocycle. The tagged derivatives indicated in protein pull-down assays that they bind to Hsp90 at the same binding site (N-Middle domain) as the San A-amide peptide. Further, these compounds inhibit binding between Hsp90 and multiple C-terminal client proteins. This interaction is unique to the San A analogs indicating they can be tuned for selectivity against Hsp90 client/co-chaperone proteins.
authors.affiliation: Department of Chemistry and Biochemistry, 5500 Campanile Drive, San Diego State University, San Diego, CA 92182-1030, United States.
authors.forename: Joseph B
authors.initials: JB
authors.lastname: Kunicki
authors.forename: Mark N
authors.initials: MN
authors.lastname: Petersen
authors.forename: Leslie D
authors.initials: LD
authors.lastname: Alexander
authors.forename: Veronica C
authors.initials: VC
authors.lastname: Ardi
authors.forename: Jeanette R
authors.initials: JR
authors.lastname: McConnell
authors.forename: Shelli R
authors.initials: SR
authors.lastname: McAlpine
mesh_terms: D001665:Binding Sites / Q000187:drug effects; D001710:Biotin / Q000737:chemistry*; D047630:Depsipeptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors*; D008968:Molecular Conformation; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D047630:Depsipeptides; D018841:HSP90 Heat-Shock Proteins; C119376:sansalvamide A; D001710:Biotin