| Title : Discovery of non-covalent dipeptidyl peptidase IV inhibitors which induce a conformational change in the active site - Sheehan_2007_Bioorg.Med.Chem.Lett_17_1765 |
| Author(s) : 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 |
| Ref : Bioorganic & Medicinal Chemistry Lett , 17 :1765 , 2007 |
|
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. |
| PubMedSearch : Sheehan_2007_Bioorg.Med.Chem.Lett_17_1765 |
| PubMedID: 17239592 |
| Gene_locus related to this paper: human-DPP4 |
| Inhibitor | Lilly-aryl-ketone |
| Gene_locus | human-DPP4 |
| Structure | 2OGZ |
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 (2007)
Discovery of non-covalent dipeptidyl peptidase IV inhibitors which induce a conformational change in the active site
Bioorganic & Medicinal Chemistry Lett
17 :1765
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 (2007)
Bioorganic & Medicinal Chemistry Lett
17 :1765