Probing the Bioactive Conformation of an Archetypal Natural Product HDAC Inhibitor with Conformationally Homogeneous Triazole‐Modified Cyclic Tetrapeptides

Abstract
Fooling enzymes with mock amides: Analogues of apicidin, a cyclic‐tetrapeptide inhibitor of histone deacetylase (HDAC), were designed with a 1,4‐ or 1,5‐disubstituted 1,2,3‐triazole in place of a backbone amide bond to fix the bond in question in either a trans‐like or a cis‐like configuration. Thus, the binding affinity of distinct peptide conformations (see picture) could be probed. One analogue proved in some cases to be superior to apicidin as an HDAC inhibitor.

This publication has 68 references indexed in Scilit: