Red fluorescent scaffold for highly sensitive protease activity probes

Yu Kushida; Kenjiro Hanaoka; Toru Komatsu; Takuya Terai; Tasuku Ueno; Kengo Yoshida; Masanobu Uchiyama; Tetsuo Nagano

doi:10.1016/j.bmcl.2012.04.114

Red fluorescent scaffold for highly sensitive protease activity probes

Yu Kushida, Kenjiro Hanaoka, Toru Komatsu, Takuya Terai, Tasuku Ueno, Kengo Yoshida, Masanobu Uchiyama, Tetsuo Nagano

Research output: Contribution to journal › Article › peer-review

40 Citations (Scopus)

Abstract

We have developed a novel red fluorescent dye, 2Me SiR600 (λ_em = 613 nm), in which the O atom of Rhodamine Green at the 10 position of the xanthene moiety is replaced with a Si atom, as a scaffold for probes to detect protease activity with extremely high S/N ratio. As proof of concept, we designed and synthesized probes for caspase-3 activity (Z-DEVD-SiR600) and leucine aminopeptidase activity (Leu-SiR600). Caspase-3-mediated cleavage of Z-DEVD-SiR600 resulted in a large bathochromic shift (93 nm) of the absorption maximum and a 432-fold fluorescence enhancement.

Original language	English
Pages (from-to)	3908-3911
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	22
Issue number	12
DOIs	https://doi.org/10.1016/j.bmcl.2012.04.114
Publication status	Published - 2012 Jun 15
Externally published	Yes

Keywords

Enzymes
Fluorescent probes
Proteases

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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10.1016/j.bmcl.2012.04.114

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title = "Red fluorescent scaffold for highly sensitive protease activity probes",

abstract = "We have developed a novel red fluorescent dye, 2Me SiR600 (λem = 613 nm), in which the O atom of Rhodamine Green at the 10 position of the xanthene moiety is replaced with a Si atom, as a scaffold for probes to detect protease activity with extremely high S/N ratio. As proof of concept, we designed and synthesized probes for caspase-3 activity (Z-DEVD-SiR600) and leucine aminopeptidase activity (Leu-SiR600). Caspase-3-mediated cleavage of Z-DEVD-SiR600 resulted in a large bathochromic shift (93 nm) of the absorption maximum and a 432-fold fluorescence enhancement.",

keywords = "Enzymes, Fluorescent probes, Proteases",

author = "Yu Kushida and Kenjiro Hanaoka and Toru Komatsu and Takuya Terai and Tasuku Ueno and Kengo Yoshida and Masanobu Uchiyama and Tetsuo Nagano",

note = "Funding Information: This research was supported in part by the Ministry of Education, Culture, Sports, Science and Technology of Japan (Specially Promoted Research Grant Nos. 22000006 to T.N., and 24659042 to K.H.), SENTAN, JST to K.H. K.H. was also supported by Inoue Foundation for Science, Takeda Science Foundation, Grant-in-Aid from the Tokyo Biochemical Research Foundation, Konica Minolta Science and Technology Foundation, The Asahi Glass Foundation and Astellas Foundation for Research on Metabolic Disorders. ",

year = "2012",

month = jun,

day = "15",

doi = "10.1016/j.bmcl.2012.04.114",

language = "English",

volume = "22",

pages = "3908--3911",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

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number = "12",

}

TY - JOUR

T1 - Red fluorescent scaffold for highly sensitive protease activity probes

AU - Kushida, Yu

AU - Hanaoka, Kenjiro

AU - Komatsu, Toru

AU - Terai, Takuya

AU - Ueno, Tasuku

AU - Yoshida, Kengo

AU - Uchiyama, Masanobu

AU - Nagano, Tetsuo

N1 - Funding Information: This research was supported in part by the Ministry of Education, Culture, Sports, Science and Technology of Japan (Specially Promoted Research Grant Nos. 22000006 to T.N., and 24659042 to K.H.), SENTAN, JST to K.H. K.H. was also supported by Inoue Foundation for Science, Takeda Science Foundation, Grant-in-Aid from the Tokyo Biochemical Research Foundation, Konica Minolta Science and Technology Foundation, The Asahi Glass Foundation and Astellas Foundation for Research on Metabolic Disorders.

PY - 2012/6/15

Y1 - 2012/6/15

N2 - We have developed a novel red fluorescent dye, 2Me SiR600 (λem = 613 nm), in which the O atom of Rhodamine Green at the 10 position of the xanthene moiety is replaced with a Si atom, as a scaffold for probes to detect protease activity with extremely high S/N ratio. As proof of concept, we designed and synthesized probes for caspase-3 activity (Z-DEVD-SiR600) and leucine aminopeptidase activity (Leu-SiR600). Caspase-3-mediated cleavage of Z-DEVD-SiR600 resulted in a large bathochromic shift (93 nm) of the absorption maximum and a 432-fold fluorescence enhancement.

AB - We have developed a novel red fluorescent dye, 2Me SiR600 (λem = 613 nm), in which the O atom of Rhodamine Green at the 10 position of the xanthene moiety is replaced with a Si atom, as a scaffold for probes to detect protease activity with extremely high S/N ratio. As proof of concept, we designed and synthesized probes for caspase-3 activity (Z-DEVD-SiR600) and leucine aminopeptidase activity (Leu-SiR600). Caspase-3-mediated cleavage of Z-DEVD-SiR600 resulted in a large bathochromic shift (93 nm) of the absorption maximum and a 432-fold fluorescence enhancement.

KW - Enzymes

KW - Fluorescent probes

KW - Proteases

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M3 - Article

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AN - SCOPUS:84861570684

SN - 0960-894X

VL - 22

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EP - 3911

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 12

ER -

Red fluorescent scaffold for highly sensitive protease activity probes

Abstract

Keywords

ASJC Scopus subject areas

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