Discovery of new binding elements in DPP-4 inhibition and their applications in novel DPP-4 inhibitor design

Probing with tool molecules, and by modeling and X-ray crystallography the binding modes of two structurally distinct series of DPP-4 inhibitors led to the discovery of a rare aromatic fluorine H-bond and the spatial requirement for better biaryl binding in the DPP-4 enzyme active site. These newly found binding elements were successfully incorporated into novel DPP-4 inhibitors.

Graphical abstractThe newly discovered aromatic fluorine H-bond and other binding elements in the DPP-4 inhibition were successfully incorporated into novel DPP-4 inhibitors such as 20a.Figure optionsDownload full-size imageDownload as PowerPoint slide