Establishment of Molecular Design Strategy To Obtain Activatable Fluorescent Probes for Carboxypeptidases

Authors:
Publisher website
Google Scholar
Abstract
Carboxypeptidases (CPs) are a family of hydrolases that cleave one or more amino acids from the C-terminal of peptides or proteins. However, methodology to monitor the activities of CPs is poorly developed. Here, we present the first versatile design strategy to obtain activatable fluorescent probes for CPs by utilizing intramolecular spirocyclization of rhodamine to translate the “aliphatic carboxamide to aliphatic carboxylate” structural conversion catalyzed by CPs into dynamic fluorescence activation. Based on this novel strategy, we developed probes for carboxypeptidases A and B. One of these probes was able to detect pancreatic juice leakage in mice ex vivo, suggesting that its suitability for intraoperative diagnosis of pancreatic fistula. This design strategy should be broadly applicable to CPs, as well as other previously untargetable enzymes, enabling development of fluorescent probes to study various pathological and biological processes.
Funding Information
  • Japan Agency for Medical Research and Development
  • Japan Foundation for Applied Enzymology
  • Japan Society for the Promotion of Science (16H06574, 16J09996, JP15H05951, JP16H02606, JP26111012)
  • Japan Science and Technology Agency (JPMJPR14F8)
  • Hoansha Foundation

This publication has 44 references indexed in Scilit: