Peptidyl-prolyl isomerase inhibitors.
Designed peptidyl-prolyl isomerase (PPIase) inhibitors of Pin1, cyclophilin (CyP), and FK506 binding protein (FKBP) are reviewed. Emphasis is placed on the design, structure, and biological activity of the inhibitors. While CyP and FKBP inhibitors have been explored fairly thoroughly, inhibitors of the relatively new Pin1 cell cycle regulator are in their infancy. Ligands designed for Pin1 and CyP have primarily been ground state analogues: alkenes and bicyclic compounds. For FKBP, more of the focus has been on analogues of bonds at the reactive center, the prolyl amide, because of the idea that the alpha-ketoamide of FK506 is an analogue of the twisted amide in the transition state.
Wang
Xiaodong J
XJ
Department of Chemistry, Virginia Tech, Blacksburg, VA 24060, USA.
Etzkorn
Felicia A
FA
D001665:Binding Sites; D021983:Cyclophilins / Q000737:chemistry*; D004791:Enzyme Inhibitors / Q000737:chemistry*; D006801:Humans; D008024:Ligands; D015394:Molecular Structure; D019696:Peptidylprolyl Isomerase / Q000037:antagonists & inhibitors*; D011487:Protein Conformation; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D016559:Tacrolimus / Q000737:chemistry*; D022021:Tacrolimus Binding Proteins / Q000737:chemistry*
D004791:Enzyme Inhibitors; D008024:Ligands; D021983:Cyclophilins; D022021:Tacrolimus Binding Proteins; D019696:Peptidylprolyl Isomerase; D016559:Tacrolimus