Nanomolar Inhibitors of the Peptidyl Prolyl Cis/Trans Isomerase Pin1 from Combinatorial Peptide Libraries

作者：Dirk Wildemann, Frank Erdmann, Birte Hernandez Alvarez, Gerlind Stoller, Xiao Zhen Zhou, Jörg Fanghänel, Mike Schutkowski, Kun Ping Lu, Gunter S. Fischer · 发表于：Journal of Medicinal Chemistry · 年份：2006 · DOI：10.1021/jm060036n · 被引用次数：89 · 研究领域：Signaling Pathways in Disease、Peptidase Inhibition and Analysis

The peptidyl prolyl cis/trans isomerase Pin1 has been implicated in the development of cancer, Alzheimer's disease and asthma, but highly specific and potent Pin1 inhibitors remain to be identified. Here, by screening a combinatorial peptide library, we identified a series of nanomolar peptidic inhibitors. Nonproteinogenic amino acids, incorporated into 5-mer to 8-mer oligopeptides containing a d-phosphothreonine as a central template, yielded selective inhibitors that blocked cell cycle progression in HeLa cells in a dose-dependent manner.