Discovery of non-covalent dipeptidyl peptidase IV inhibitors which induce a conformational change in the active site.
Article Details
- CitationCopy to clipboard
Sheehan SM, Mest HJ, Watson BM, Klimkowski VJ, Timm DE, Cauvin A, Parsons SH, Shi Q, Canada EJ, Wiley MR, Ruehter G, Evers B, Petersen S, Blaszczak LC, Pulley SR, Margolis BJ, Wishart GN, Renson B, Hankotius D, Mohr M, Zechel JC, Michael Kalbfleisch J, Dingess-Hammond EA, Boelke A, Weichert AG
Discovery of non-covalent dipeptidyl peptidase IV inhibitors which induce a conformational change in the active site.
Bioorg Med Chem Lett. 2007 Mar 15;17(6):1765-8. Epub 2006 Dec 24.
- PubMed ID
- 17239592 [ View in PubMed]
- Abstract
A series of non-covalent inhibitors of the serine protease dipeptidyl peptidase IV (DPP-IV) were found to adopt a U-shaped binding conformation in X-ray co-crystallization studies. Remarkably, Tyr547 undergoes a 70 degrees side-chain rotation to accommodate the inhibitor and allows access to a previously unexposed area of the protein backbone for hydrogen bonding.
DrugBank Data that Cites this Article
- Binding Properties
Drug Target Property Measurement pH Temperature (°C) 4-[(3R)-3-{[2-(4-FLUOROPHENYL)-2-OXOETHYL]AMINO}BUTYL]BENZAMIDE Dipeptidyl peptidase 4 IC 50 (nM) 84 7.5 22 Details