A NIR fluorescent probe for Vanin-1 and its applications in imaging, kidney injury diagnosis, and the development of inhibitor

Vanin-1 is an amidohydrolase that catalyses the conversion of pantetheine into the amino-thiol cysteamine and pantothenic acid (coenzyme A precursor), which plays a vital role in multiple physiological and pathological processes. In this study, an enzyme-activated near-infrared (NIR) fluorescent probe (DDAV) has been constructed for sensitively detecting Vanin-1 activity in complicated biosamples on the basis of its catalytic characteristics. DDAV exhibited a high selectivity and sensitivity toward Vanin-1 and was successfully applied to the early diagnosis of kidney injury in cisplatin-induced kidney injury model. In addition, DDAV could serve as a visual tool for in situ imaging endogenous Vanin-1 in vivo. More importantly, Enterococcus faecalis 20247 which possessed high expression of Vanin-1 was screened out from intestinal bacteria using DDAV, provided useful guidance for the rational use of NSAIDs in clinic. Finally, oleuropein as a potent natural inhibitor for Vanin-1 was discovered from herbal medicines library using a high-throughput screening method using DDAV, which held great promise for clinical therapy of inflammatory bowel disease. (C) 2022 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.

Automated summary

An enzyme-activated NIR fluorescent probe (DDAV) was constructed to detect Vanin-1 activity in biosamples with high selectivity and sensitivity, allowing for early diagnosis of kidney injury and visualization of endogenous Vanin-1 in vivo. Screening of intestinal bacteria with high Vanin-1 expression using DDAV provided guidance for NSAIDs use, while oleuropein was identified as a potent natural inhibitor for Vanin-1, showing promise for clinical therapy of inflammatory bowel disease.