Synthesis of Firefly Luciferin Analogues and Evaluation of the Luminescent Properties

Shuji Ioka; Tsuyoshi Saitoh; Satoshi Iwano; Koji Suzuki; Shojiro A. Maki; Atsushi Miyawaki; Masaya Imoto; Shigeru Nishiyama

doi:10.1002/chem.201600278

Synthesis of Firefly Luciferin Analogues and Evaluation of the Luminescent Properties

Shuji Ioka, Tsuyoshi Saitoh, Satoshi Iwano, Koji Suzuki, Shojiro A. Maki, Atsushi Miyawaki, Masaya Imoto, Shigeru Nishiyama

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

21 Citations (Scopus)

Abstract

Five new firefly luciferin (1) analogues were synthesized and their light emission properties were examined. Modifications of the thiazoline moiety in 1 were employed to produce analogues containing acyclic amino acid side chains (2–4) and heterocyclic rings derived from amino acids (5 and 6) linked to the benzothiazole moiety. Although methyl esters of all of the synthetic derivatives exhibited chemiluminescence activity, only carboluciferin (6), possessing a pyrroline-substituted benzothiazole structure, had bioluminescence (BL) activity (λ_max=547 nm). Results of bioluminescence studies with AMP-carboluciferin (AMP=adenosine monophosphate) and AMP-firefly luciferin showed that the nature of the thiazoline mimicking moiety affected the adenylation step of the luciferin–luciferase reaction required for production of potent BL. In addition, BL of 6 in living mice differed from that of 1 in that its luminescence decay rate was slower.

Original language	English
Pages (from-to)	9330-9337
Number of pages	8
Journal	Chemistry - A European Journal
Volume	22
Issue number	27
DOIs	https://doi.org/10.1002/chem.201600278
Publication status	Published - 2016 Jun 27

Keywords

biological activity
firefly luciferase
luminescence
structure–activity relationships
synthesis design

ASJC Scopus subject areas

Catalysis
Organic Chemistry

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10.1002/chem.201600278

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title = "Synthesis of Firefly Luciferin Analogues and Evaluation of the Luminescent Properties",

abstract = "Five new firefly luciferin (1) analogues were synthesized and their light emission properties were examined. Modifications of the thiazoline moiety in 1 were employed to produce analogues containing acyclic amino acid side chains (2–4) and heterocyclic rings derived from amino acids (5 and 6) linked to the benzothiazole moiety. Although methyl esters of all of the synthetic derivatives exhibited chemiluminescence activity, only carboluciferin (6), possessing a pyrroline-substituted benzothiazole structure, had bioluminescence (BL) activity (λmax=547 nm). Results of bioluminescence studies with AMP-carboluciferin (AMP=adenosine monophosphate) and AMP-firefly luciferin showed that the nature of the thiazoline mimicking moiety affected the adenylation step of the luciferin–luciferase reaction required for production of potent BL. In addition, BL of 6 in living mice differed from that of 1 in that its luminescence decay rate was slower.",

keywords = "biological activity, firefly luciferase, luminescence, structure–activity relationships, synthesis design",

author = "Shuji Ioka and Tsuyoshi Saitoh and Satoshi Iwano and Koji Suzuki and Maki, {Shojiro A.} and Atsushi Miyawaki and Masaya Imoto and Shigeru Nishiyama",

note = "Funding Information: This study was partially supported by the Japan Student Services Organization, JSPS KAKENHI Grant Number 24225001, and Keio Leading-Edge Laboratory of Science and Technology. Prof. Dr. Daniel Citterio gave us constructive comments and warm encouragement.",

year = "2016",

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doi = "10.1002/chem.201600278",

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T1 - Synthesis of Firefly Luciferin Analogues and Evaluation of the Luminescent Properties

AU - Ioka, Shuji

AU - Saitoh, Tsuyoshi

AU - Iwano, Satoshi

AU - Suzuki, Koji

AU - Maki, Shojiro A.

AU - Miyawaki, Atsushi

AU - Imoto, Masaya

AU - Nishiyama, Shigeru

N1 - Funding Information: This study was partially supported by the Japan Student Services Organization, JSPS KAKENHI Grant Number 24225001, and Keio Leading-Edge Laboratory of Science and Technology. Prof. Dr. Daniel Citterio gave us constructive comments and warm encouragement.

PY - 2016/6/27

Y1 - 2016/6/27

N2 - Five new firefly luciferin (1) analogues were synthesized and their light emission properties were examined. Modifications of the thiazoline moiety in 1 were employed to produce analogues containing acyclic amino acid side chains (2–4) and heterocyclic rings derived from amino acids (5 and 6) linked to the benzothiazole moiety. Although methyl esters of all of the synthetic derivatives exhibited chemiluminescence activity, only carboluciferin (6), possessing a pyrroline-substituted benzothiazole structure, had bioluminescence (BL) activity (λmax=547 nm). Results of bioluminescence studies with AMP-carboluciferin (AMP=adenosine monophosphate) and AMP-firefly luciferin showed that the nature of the thiazoline mimicking moiety affected the adenylation step of the luciferin–luciferase reaction required for production of potent BL. In addition, BL of 6 in living mice differed from that of 1 in that its luminescence decay rate was slower.

AB - Five new firefly luciferin (1) analogues were synthesized and their light emission properties were examined. Modifications of the thiazoline moiety in 1 were employed to produce analogues containing acyclic amino acid side chains (2–4) and heterocyclic rings derived from amino acids (5 and 6) linked to the benzothiazole moiety. Although methyl esters of all of the synthetic derivatives exhibited chemiluminescence activity, only carboluciferin (6), possessing a pyrroline-substituted benzothiazole structure, had bioluminescence (BL) activity (λmax=547 nm). Results of bioluminescence studies with AMP-carboluciferin (AMP=adenosine monophosphate) and AMP-firefly luciferin showed that the nature of the thiazoline mimicking moiety affected the adenylation step of the luciferin–luciferase reaction required for production of potent BL. In addition, BL of 6 in living mice differed from that of 1 in that its luminescence decay rate was slower.

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Synthesis of Firefly Luciferin Analogues and Evaluation of the Luminescent Properties

Abstract

Keywords

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