title: Discovery and binding studies on a series of novel Pin1 ligands.
abstract: 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.
authors.affiliation: Infectious and Inflammatory Disease Center and Cancer Center, Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Bainan
authors.initials: B
authors.lastname: Wu
authors.forename: Michele F
authors.initials: MF
authors.lastname: Rega
authors.forename: Jun
authors.initials: J
authors.lastname: Wei
authors.forename: Hongbin
authors.initials: H
authors.lastname: Yuan
authors.forename: Russell
authors.initials: R
authors.lastname: Dahl
authors.forename: Ziming
authors.initials: Z
authors.lastname: Zhang
authors.forename: Maurizio
authors.initials: M
authors.lastname: Pellecchia
mesh_terms: D003198:Computer Simulation; D004926:Escherichia coli / Q000235:genetics; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D019696:Peptidylprolyl Isomerase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D021281:Quantitative Structure-Activity Relationship; D012694:Serine / Q000737:chemistry / Q000378:metabolism; D054852:Small Molecule Libraries / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D008024:Ligands; D054852:Small Molecule Libraries; D012694:Serine; D019696:Peptidylprolyl Isomerase