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

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:21

Article

Kunicki, Joseph B.²  Petersen, Mark N.²  Alexander, Leslie D.²  Ardi, Veronica C.²  McConnell, Jeanette R.²  McAlpine, Shelli R.¹ 

[1] Univ New S Wales, Dept Chem, Sydney, NSW 2052, Australia

[2] San Diego State Univ, Dept Chem & Biochem, San Diego, CA 92182 USA

关键词: Sansalvamide A;    Hsp90;    N-Middle domain;   

DOI  :  10.1016/j.bmcl.2011.06.083

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

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