Nanomolar inhibitors of the peptidyl prolyl cis/trans isomerase Pin1 from combinatorial peptide libraries.
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.
Max Planck Research Unit for Enzymology of Protein Folding, Weinbergweg 22, 06120 Halle/Saale, Germany.
Dirk
D
Wildemann
Frank
F
Erdmann
Birte Hernandez
BH
Alvarez
Gerlind
G
Stoller
Xiao Z
XZ
Zhou
Jörg
J
Fanghänel
Mike
M
Schutkowski
Kun P
KP
Lu
Gunter
G
Fischer
D020134:Catalytic Domain; D020650:Combinatorial Chemistry Techniques; D006367:HeLa Cells; D006801:Humans; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D009842:Oligopeptides / Q000737:chemistry* / Q000494:pharmacology; D019696:Peptidylprolyl Isomerase / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D011485:Protein Binding; D017434:Protein Structure, Tertiary
D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D009842:Oligopeptides; C000606846:PIN1 protein, human; D019696:Peptidylprolyl Isomerase