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Nanomolar inhibitors of the peptidyl prolyl cis/trans isomerase Pin1 from combinatorial peptide libraries

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Hernandez Alvarez,  B       
Department Protein Evolution, Max Planck Institute for Developmental Biology, Max Planck Society;

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Citation

Wildemann, D., Erdmann, F., Hernandez Alvarez, B., Stoller, G., Zhou, X., Fanghänel, J., et al. (2006). Nanomolar inhibitors of the peptidyl prolyl cis/trans isomerase Pin1 from combinatorial peptide libraries. Journal of Medicinal Chemistry, 49(7), 2147-2150. doi:10.1021/jm060036n.


Cite as: https://hdl.handle.net/21.11116/0000-000B-A783-4
Abstract
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.