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
N1 - Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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
UR - http://www.scopus.com/inward/record.url?scp=85140612309&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85140612309&partnerID=8YFLogxK
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 -