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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.

SUBMITTER: Kunicki JB

PROVIDER: S-EPMC3155875 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature

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

Kunicki Joseph B JB Petersen Mark N MN Alexander Leslie D LD Ardi Veronica C VC McConnell Jeanette R JR McAlpine Shelli R SR

Bioorganic & medicinal chemistry letters 20110625 16

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 ...[more]

PMID: 21764310

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