Tailored fragments of roseophilin selectively antagonize Mcl-1 in vitro

TETRAHEDRON LETTERS

卷:56

Article

Bracken, Jack D.¹  Carlson, Andrew D.¹  Frederich, James H.¹  Nguyen, Mai^2,3  Shore, Gordon C.^2,3  Harran, Patrick G.¹ 

[1] Univ Calif Los Angeles, Dept Chem & Biochem, Los Angeles, CA 90095 USA

[2] McGill Univ, Dept Biochem, Montreal, PQ, Canada

[3] McGill Univ, Goodman Canc Res Ctr, Montreal, PQ, Canada

关键词: Roseophilin;    Mcl-1;    Bcl-2;    Tetrazole;    Obatoclax;   

DOI  :  10.1016/j.tetlet.2015.01.191

来源: Elsevier

【 摘 要 】

We have discovered a fragment of the natural product roseophilin, a member of the prodiginine family, that antagonizes Mcl-1 functions in a liposome-based assay for mitochondrial membrane permeabilization. By tailoring this substance such that it can participate in salt bridging with the protein surface, we have prepared the first prodiginine inspired structure that shows direct, saturable binding to a recombinant Bcl-2 family member in vitro. (C) 2015 Elsevier Ltd. All rights reserved.

【 授权许可】

Free