New luciferin-based probe substrates for human CYP26A1

• Main Authors: Shishir Sharma, Jingyao Liu, Xue Zhang, Sangeeta Shrestha Sharma, Erik J. Sorensen, Matthias Bureik
• Format: Article
• Language: English
• Published: Elsevier 2020-12-01
• Series: Biochemistry and Biophysics Reports
• Subjects: CYP enzymes; Esters; Fission yeast; Luminescent probe; Retinoic acid
• Online Access: http://www.sciencedirect.com/science/article/pii/S2405580820301710
• ISSN: 2405-5808

Activity of human CYP26A1 towards six proluciferin probe substrates and their ester derivatives was monitored. These included three monofluorobenzyl ether isomers and three five-membered heterocycles. Overall, luciferin substrates with a free acid group gave higher activities than the ester compounds. Also, luciferin derivatives with six-ring structures were better metabolized than those with five-rings. The best substrates identified in this study are Luciferin 6′ 3-fluorobenzyl ether (Luciferin-3FBE) and its methyl ester (Luciferin-3FBEME). Taken together, we describe eleven new probe substrates for CYP26A1 and demonstrate for the first time that CYP26A1 does not only accept acid substrates but can also metabolize esters.