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

doi:10.1021/jacs.7b11014

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 journal › Article › peer-review

41 Citations (Scopus)

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.

Original language	English
Pages (from-to)	1767-1773
Number of pages	7
Journal	Journal of the American Chemical Society
Volume	140
Issue number	5
DOIs	https://doi.org/10.1021/jacs.7b11014
Publication status	Published - 2018 Feb 7
Externally published	Yes

ASJC Scopus subject areas

Catalysis
Chemistry(all)
Biochemistry
Colloid and Surface Chemistry

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10.1021/jacs.7b11014

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@article{3cfbc9872610409a97a40345f1d44bdf,

title = "Establishment of Molecular Design Strategy to Obtain Activatable Fluorescent Probes for Carboxypeptidases",

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.",

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

note = "Funding Information: †Graduate School of Pharmaceutical Sciences and ‡Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan §PRESTO (Japan) Science and Technology Agency (JST), 4-1-8 Honcho Kawaguchi-shi, Saitama 332-0012, Japan ∥Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto, 602-8566, Japan ⊥Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo 135-8550, Japan #Department of Surgery, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan ⊗CREST (Japan) Agency for Medical Research and Development (AMED), 1-7-1 Otemachi, Chiyoda-ku, Tokyo 100-0004, Japan Funding Information: We thank Dr. Takuya Myochin, Dr. Hiroki Ito, Dr. Shinpei Iwaki, Dr. Yu Kagami, and Dr. Shodai Takahashi for valuable discussions. This research was supported in part by AMED-CREST, by JST/PRESTO Grant No. JPMJPR14F8 (to M.K.), by MEXT/JSPS KAKENHI Grant Nos. JP16H02606 and JP26111012 (to Y.U.), 16H06574 (to T.U.), by JP15H05951“Resonance Bio” (to M.K.), by JSPS Core-to-Core Program, A, Advanced Research Networks (to Y.U.), by the Project for Cancer Research And Therapeutic Evolution (P-CREATE) from the Japan Agency for Medical Research and development, AMED (to Y.U.), by a grant from Hoansha Foundation (to Y.U.), by a grant from Japan Foundation for Applied Enzymology (to M.K.), and by a Grant-in-Aid for JSPS Fellows (16J09996) (to Y.K.). Publisher Copyright: {\textcopyright} 2018 American Chemical Society.",

year = "2018",

month = feb,

day = "7",

doi = "10.1021/jacs.7b11014",

language = "English",

volume = "140",

pages = "1767--1773",

journal = "Journal of the American Chemical Society",

issn = "0002-7863",

publisher = "American Chemical Society",

number = "5",

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T1 - Establishment of Molecular Design Strategy to Obtain Activatable Fluorescent Probes for Carboxypeptidases

AU - Kuriki, Yugo

AU - Kamiya, Mako

AU - Kubo, Hidemasa

AU - Komatsu, Toru

AU - Ueno, Tasuku

AU - Tachibana, Ryo

AU - Hayashi, Kento

AU - Hanaoka, Kenjiro

AU - Yamashita, Suguru

AU - Ishizawa, Takeaki

AU - Kokudo, Norihiro

AU - Urano, Yasuteru

N1 - Funding Information: †Graduate School of Pharmaceutical Sciences and ‡Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan §PRESTO (Japan) Science and Technology Agency (JST), 4-1-8 Honcho Kawaguchi-shi, Saitama 332-0012, Japan ∥Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto, 602-8566, Japan ⊥Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo 135-8550, Japan #Department of Surgery, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan ⊗CREST (Japan) Agency for Medical Research and Development (AMED), 1-7-1 Otemachi, Chiyoda-ku, Tokyo 100-0004, Japan Funding Information: We thank Dr. Takuya Myochin, Dr. Hiroki Ito, Dr. Shinpei Iwaki, Dr. Yu Kagami, and Dr. Shodai Takahashi for valuable discussions. This research was supported in part by AMED-CREST, by JST/PRESTO Grant No. JPMJPR14F8 (to M.K.), by MEXT/JSPS KAKENHI Grant Nos. JP16H02606 and JP26111012 (to Y.U.), 16H06574 (to T.U.), by JP15H05951“Resonance Bio” (to M.K.), by JSPS Core-to-Core Program, A, Advanced Research Networks (to Y.U.), by the Project for Cancer Research And Therapeutic Evolution (P-CREATE) from the Japan Agency for Medical Research and development, AMED (to Y.U.), by a grant from Hoansha Foundation (to Y.U.), by a grant from Japan Foundation for Applied Enzymology (to M.K.), and by a Grant-in-Aid for JSPS Fellows (16J09996) (to Y.K.). Publisher Copyright: © 2018 American Chemical Society.

PY - 2018/2/7

Y1 - 2018/2/7

N2 - 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.

AB - 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.

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DO - 10.1021/jacs.7b11014

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JF - Journal of the American Chemical Society

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ER -

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

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