Synthesis of proteogenic amino acid-based NAD analogs

Nicotinamide adenine dinucleotide (NAD) analogs have been prepared for diverse applications especially as alternative redox cofactors for NAD-dependent enzymes. Herein, 14 NAD analogs based on proteogenic amino acids were synthesized in 20-98% isolated yields through the Zincke reaction in the presence of triethylamine. Their physicochemical properties including spectroscopy and redox potential were characterized. Preliminary activity screening results showed that a few reduced analogs were effective as cofactors for a mutant cytochrome P450 enzyme to facilitate fatty acid hydroxylation. (C) 2021 Elsevier Ltd. All rights reserved.

Automated summary

Fourteen NAD analogs based on proteogenic amino acids were synthesized with isolated yields ranging from 20-98% through the Zincke reaction in the presence of triethylamine. Some of the reduced analogs were found to effectively act as cofactors for a mutant cytochrome P450 enzyme to facilitate fatty acid hydroxylation.