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Discovery and Binding Studies on a Series of Novel Pin1 Ligands
Author(s) -
Wu Bainan,
Rega Michele F.,
Wei Jun,
Yuan Hongbin,
Dahl Russell,
Zhang Ziming,
Pellecchia Maurizio
Publication year - 2009
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/j.1747-0285.2009.00795.x
Subject(s) - pin1 , drug discovery , chemistry , computational biology , fkbp , serine , peptidylprolyl isomerase , small molecule , nuclear magnetic resonance spectroscopy , combinatorial chemistry , biochemistry , stereochemistry , biology , phosphorylation , isomerase , enzyme
Pin1 plays a key role in various biological cellular processes via the recognition of phosphorylated Ser/Thr‐Proline motifs. Moreover, high expression levels of Pin1 are correlated to tumorgenesis in some cancer types. Here, we identify a novel series of small molecular weight compounds with a core structure mimicking the phoshorylated serine. The binding affinity and binding mode of the compounds for Pin1 are analyzed via NMR spectroscopy and computational studies. The reported chemical probes and relative binding data to Pin1 represent valuable stepping stones for the validation of Pin1 as target for drug discovery and for eventually the development of possible lead compounds.