An optimized NIR fluorescent probe for visualizing DPP IV and applications in the diagnosis and therapy of inflammatory bowel diseases

Dipeptidyl peptidase IV (DPP IV), is a membrane glycoprotein with exopeptidase activity, that mediates the degradation of glucagon-like-1 (GLP-1) and plays a vital role in diabetes and inflammatory bowel diseases (IBD). In the present work, a highly selective near-infrared (NIR) fluorescent probe DSACD was developed for DPP IV, which exhibited excellent fluorescence properties with high selectivity and affinity toward DPP IV. Using DSACD realized the real-time imaging of DPPIV in various living cells and organs. Importantly, the significant upregulation of DPPIV in intestine was found during the development of IBD via visual imaging and further validated by western blot. At last, DSACD was used for the high-throughput screening the inhibitory effects of 150 kinds common herbs toward DPP IV. Demethoxycurcumin as a novel natural inhibitor for DPP IV was discovered from Curcuma Longa. Furthermore, Demethoxycurcumin exhibited an excellent bioactivity in vivo for the treatment of DSS-induced IBD. In summary, DSACD could serve as a promising tool not only for real-time visual monitoring and exploring the physiological function of DPP IV, but also provided a practical approach for rapid discovery of new potential inhibitors toward DPP IV for treatment of IBD in clinic.