Discovery of non-covalent dipeptidyl peptidase IV inhibitors which induce a conformational change in the active site
- 作者：Scott M. Sheehan ; Hans-Juergen Mest ; Brian M. Watson ; Valentine J. Klimkowski ; David E. Timm ; Annick Cauvin ; Stephen H. Parsons ; Qing Shi ; Emily J. Canada ; Michael R. Wiley ; et al.
- 关键词：Dipeptidyl peptidase IV ; Protease inhibitor ; X-ray co-crystal structure ; Oral glucose tolerance test
- 刊名：Bioorganic and Medicinal Chemistry Letters
- 出版年：2007
- 期刊代码：10_0960894x
- 类别：ch
- 出版时间：15 March 2007
- 卷：17
- 期：6
- 页码：1765-1768
- 文件大小：371 K
摘要
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° side-chain rotation to accommodate the inhibitor and allows access to a previously unexposed area of the protein backbone for hydrogen bonding.