Synthesis and evaluation of biotinylated sansalvamide A analogs and their modulation of Hsp90

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. (C) 2011 Elsevier Ltd. All rights reserved.