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

Yugo Kuriki, Mako Kamiya, Hidemasa Kubo, Toru Komatsu, Tasuku Ueno, Ryo Tachibana, Kento Hayashi, Kenjiro Hanaoka, Suguru Yamashita, Takeaki Ishizawa, Norihiro Kokudo, Yasuteru Urano

Research output: Contribution to journalArticlepeer-review

49 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)1767-1773
Number of pages7
JournalJournal of the American Chemical Society
Issue number5
Publication statusPublished - 2018 Feb 7
Externally publishedYes

ASJC Scopus subject areas

  • Catalysis
  • General Chemistry
  • Biochemistry
  • Colloid and Surface Chemistry


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