Rational design of cyclic peptide modulators of the transcriptional coactivator CBP: a new class of p53 inhibitors.

ABSTRACT: The CREB binding protein (CBP) is a human transcriptional coactivator consisting of several conserved functional modules, which interacts with distinct transcription factors including nuclear receptors, CREB, and STAT proteins. Despite the importance of CBP in transcriptional regulation, many questions regarding the role of its particular domains in CBP functions remain unanswered. Therefore, developing small molecules capable of selectively modulating a single domain of CBP is of invaluable aid at unraveling its prominent activities. Here we report the design, synthesis, and biological evaluation of conformationally restricted peptides as novel modulators for the acetyl-lysine binding bromodomain (BRD) of CBP. Utilizing a target structure-guided and computer-aided rational design approach

SUBMITTER: Gerona-Navarro G 

PROVIDER: S-EPMC3047509 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature