Exploring the Chemical Space of Proluciferins as Probe Substrates for Human Cytochrome P450 Enzymes

Jie Zhao; Xue Zhang; Yueyin Wang; Huimin Huang; Shishir Sharma; Sangeeta Shrestha Sharma; Clemens Alexander Wolf; Sijie Liu; Gerhard Wolber; Erik J. Sorensen; Matthias Bureik

doi:10.1007/s12010-022-04184-0

Exploring the Chemical Space of Proluciferins as Probe Substrates for Human Cytochrome P450 Enzymes

Jie Zhao, Xue Zhang, Yueyin Wang, Huimin Huang, Shishir Sharma, Sangeeta Shrestha Sharma, Clemens Alexander Wolf, Sijie Liu, Gerhard Wolber, Erik J. Sorensen, Matthias Bureik

Chemistry

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

4 Scopus citations

Abstract

We report the synthesis of 21 new proluciferin compounds that bear a small aliphatic ether group connected to the 6’ hydroxy function of firefly luciferin and either contain an acid or methyl ester function at the dihydrothiazole ring. Each of these compounds was found to be a substrate for some members of the human CYP1 and CYP3 families; a total of 92 new enzyme–substrate pairs were identified. In a screen of the whole human P450 complement (CYPome) with three selected proluciferin acid substrates, another 13 enzyme–substrate pairs were detected, which involve enzymes belonging to the CYP2, CYP4, CYP7, CYP21, and CYP27 families. All in all, we identified new probe substrates for members of seven out of 18 human CYP families.

Original language	English (US)
Pages (from-to)	1042-1058
Number of pages	17
Journal	Applied Biochemistry and Biotechnology
Volume	195
Issue number	2
DOIs	https://doi.org/10.1007/s12010-022-04184-0
State	Published - Feb 2023

All Science Journal Classification (ASJC) codes

Applied Microbiology and Biotechnology
Bioengineering
Molecular Biology
Biochemistry
Biotechnology

Keywords

Chemical biology
Cytochrome P450
Probe substrate
Proluciferin

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10.1007/s12010-022-04184-0

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title = "Exploring the Chemical Space of Proluciferins as Probe Substrates for Human Cytochrome P450 Enzymes",

abstract = "We report the synthesis of 21 new proluciferin compounds that bear a small aliphatic ether group connected to the 6{\textquoteright} hydroxy function of firefly luciferin and either contain an acid or methyl ester function at the dihydrothiazole ring. Each of these compounds was found to be a substrate for some members of the human CYP1 and CYP3 families; a total of 92 new enzyme–substrate pairs were identified. In a screen of the whole human P450 complement (CYPome) with three selected proluciferin acid substrates, another 13 enzyme–substrate pairs were detected, which involve enzymes belonging to the CYP2, CYP4, CYP7, CYP21, and CYP27 families. All in all, we identified new probe substrates for members of seven out of 18 human CYP families.",

keywords = "Chemical biology, Cytochrome P450, Probe substrate, Proluciferin",

author = "Jie Zhao and Xue Zhang and Yueyin Wang and Huimin Huang and Shishir Sharma and Sharma, {Sangeeta Shrestha} and Wolf, {Clemens Alexander} and Sijie Liu and Gerhard Wolber and Sorensen, {Erik J.} and Matthias Bureik",

note = "Publisher Copyright: {\textcopyright} 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.",

year = "2023",

month = feb,

doi = "10.1007/s12010-022-04184-0",

language = "English (US)",

volume = "195",

pages = "1042--1058",

journal = "Applied Biochemistry and Biotechnology",

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TY - JOUR

T1 - Exploring the Chemical Space of Proluciferins as Probe Substrates for Human Cytochrome P450 Enzymes

AU - Zhao, Jie

AU - Zhang, Xue

AU - Wang, Yueyin

AU - Huang, Huimin

AU - Sharma, Shishir

AU - Sharma, Sangeeta Shrestha

AU - Wolf, Clemens Alexander

AU - Liu, Sijie

AU - Wolber, Gerhard

AU - Sorensen, Erik J.

AU - Bureik, Matthias

PY - 2023/2

Y1 - 2023/2

N2 - We report the synthesis of 21 new proluciferin compounds that bear a small aliphatic ether group connected to the 6’ hydroxy function of firefly luciferin and either contain an acid or methyl ester function at the dihydrothiazole ring. Each of these compounds was found to be a substrate for some members of the human CYP1 and CYP3 families; a total of 92 new enzyme–substrate pairs were identified. In a screen of the whole human P450 complement (CYPome) with three selected proluciferin acid substrates, another 13 enzyme–substrate pairs were detected, which involve enzymes belonging to the CYP2, CYP4, CYP7, CYP21, and CYP27 families. All in all, we identified new probe substrates for members of seven out of 18 human CYP families.

AB - We report the synthesis of 21 new proluciferin compounds that bear a small aliphatic ether group connected to the 6’ hydroxy function of firefly luciferin and either contain an acid or methyl ester function at the dihydrothiazole ring. Each of these compounds was found to be a substrate for some members of the human CYP1 and CYP3 families; a total of 92 new enzyme–substrate pairs were identified. In a screen of the whole human P450 complement (CYPome) with three selected proluciferin acid substrates, another 13 enzyme–substrate pairs were detected, which involve enzymes belonging to the CYP2, CYP4, CYP7, CYP21, and CYP27 families. All in all, we identified new probe substrates for members of seven out of 18 human CYP families.

KW - Chemical biology

KW - Cytochrome P450

KW - Probe substrate

KW - Proluciferin

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U2 - 10.1007/s12010-022-04184-0

DO - 10.1007/s12010-022-04184-0

M3 - Article

C2 - 36287330

AN - SCOPUS:85140612309

SN - 0273-2289

VL - 195

SP - 1042

EP - 1058

JO - Applied Biochemistry and Biotechnology

JF - Applied Biochemistry and Biotechnology

IS - 2

ER -

Exploring the Chemical Space of Proluciferins as Probe Substrates for Human Cytochrome P450 Enzymes

Abstract

All Science Journal Classification (ASJC) codes

Keywords

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