Unique binding mode of Evogliptin with human dipeptidyl peptidase IV
- Unique binding mode of Evogliptin with human dipeptidyl peptidase IV
- 김은경; 이형기; 김미경; 김하동; 김흥재; 김지원; 이지오; 김찬화
- Dipeptidyl peptidase IV; DPP4; Evogliptin; Diabetes; Inhibitor; Complex structure
- Issue Date
- Biochemical and biophysical research communications
- VOL 494, NO 3-4-459
- Evogliptin ((R)-4-((R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl)-3-(tert-butoxymethyl) piperazine-2-one)) is a highly potent selective inhibitor of dipeptidyl peptidase IV (DPP4) that was approved for the treatment of type 2 diabetes in South Korea. In this study, we report the crystal structures of Evogliptin, DA-12166, and DA-12228 (S,R diastereomer of Evogliptin) complexed to human DPP4. Analysis of both the structures and inhibitory activities suggests that the binding of the trifluorophenyl moiety in the S1 pocket and the piperazine-2-one moiety have hydrophobic interactions with Phe357 in the S2 extensive subsite, and that the multiple hydrogen bonds made by the (R)-β-amine group in the S2 pocket and the contacts made by the (R)-tert-butyl group with Arg125 contribute to the high potency observed for Evogliptin.
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