Nanomolar inhibitors of the peptidyl prolyl cis/trans isomerase Pin1 from combinatorial peptide libraries
Authors:
Wildemann D, Erdmann F, Alvarez BH, Stoller G, Zhou XZ, Fanghänel J, Schutkowski M, Lu KP, Fischer G
In:
Source:
J Med Chem
Publication Date:
(
2006
)
Issue:
49(7)
:
2147-50
Research Area:
Cancer Research/Cell Biology
Cells used in publication:
HeLa
Species: human
Tissue Origin: cervix
Platform:
Nucleofector® I/II/2b
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.
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