title: A Selective, Cell-Permeable Nonphosphorylated Bicyclic Peptidyl Inhibitor against Peptidyl-Prolyl Isomerase Pin1.
abstract: Pin1 regulates the levels and functions of phosphoproteins by catalyzing phosphorylation-dependent cis/trans isomerization of peptidyl-prolyl bonds. Previous Pin1 inhibitors contained phosphoamino acids, which are metabolically unstable and have poor membrane permeability. In this work, we report a cell-permeable and metabolically stable nonphosphorylated bicyclic peptide as a potent and selective Pin1 inhibitor, which inhibited the intracellular Pin1 activity in cultured mammalian cells but had little effect on other isomerases such as Pin4, FKBP12, or cyclophilin A.
authors.affiliation: Department of Chemistry and Biochemistry, The Ohio State University, 484 West 12th Avenue, Columbus, Ohio 43220, United States.
authors.forename: Bisheng
authors.initials: B
authors.lastname: Jiang
authors.affiliation: Department of Chemistry and Biochemistry, The Ohio State University, 484 West 12th Avenue, Columbus, Ohio 43220, United States.
authors.forename: Dehua
authors.initials: D
authors.lastname: Pei
mesh_terms: D001643:Bridged Bicyclo Compounds / Q000494:pharmacology*; D002463:Cell Membrane Permeability; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D019696:Peptidylprolyl Isomerase / Q000037:antagonists & inhibitors*; D010766:Phosphorylation
chemical_list: D001643:Bridged Bicyclo Compounds; D004791:Enzyme Inhibitors; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; C000606846:PIN1 protein, human; C000606848:PIN4 protein, human; D019696:Peptidylprolyl Isomerase