Structural and functional definition of the specificity of a novel caspase-3 inhibitor, Ac-DNLD-CHO.

ABSTRACT:

Background

The rational design of peptide-based specific inhibitors of the caspase family members using their X-ray crystallographies is an important strategy for chemical knockdown to define the critical role of each enzyme in apoptosis and inflammation. Recently, we designed a novel potent peptide inhibitor, Ac-DNLD-CHO, for caspase-3 using a new computational screening system named the Amino acid Positional Fitness (APF) method (BMC Pharmacol. 2004, 4:7). Here, we report the specificity of the DNLD sequence against caspase-3 over other major caspase family members that participate in apoptosis by computational docking and site-directed mutagenesis studies.

Results

Ac-DNLD-CHO inhibits caspases-3, -7, -8, and -9 activities with Kiapp values of 0.68, 55.7, >200, and >200 nM

SUBMITTER: Yoshimori A 

PROVIDER: S-EPMC1931592 | biostudies-literature | 2007 Jun

REPOSITORIES: biostudies-literature