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Synthesis and Biochemical Evaluation of Nicotinamide Derivatives as NADH Analogue Coenzymes in Ene Reductase
Author(s) -
Falcone Natashya,
She Zhe,
Syed Jebreil,
Lough Alan,
Kraatz HeinzBernhard
Publication year - 2019
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201800661
Subject(s) - nad+ kinase , nicotinamide , cofactor , redox , chemistry , reductase , biocatalysis , nicotinamide adenine dinucleotide , conjugate , dihydropyridine , pyridine , combinatorial chemistry , enzyme , stereochemistry , double bond , biochemistry , organic chemistry , calcium , reaction mechanism , catalysis , mathematical analysis , mathematics
Nicotinamide and pyridine‐containing conjugates have attracted a lot of attention in research as they have found use in a wide range of applications including as redox flow batteries and calcium channel blockers, in biocatalysis, and in metabolism. The interesting redox character of the compounds’ pyridine/dihydropyridine system allows them to possess very similar characteristics to the natural chiral redox agents NAD + /NADH, even mimicking their functions. There has been considerable interest in designing and synthesizing NAD + /NADH mimetics with similar redox properties. In this research, three nicotinamide conjugates were designed, synthesized, and characterized. Molecular structures obtained through X‐ray crystallography were obtained for two of the conjugates, thereby providing more detail on the bonding and structure of the compounds. The compounds were then further evaluated for biochemical properties, and it was found that one of the conjugates possessed similar functions and characteristics to the natural NADH. This compound was evaluated in the active enzyme, enoate reductase; like NADH, it was shown to help reduce the C=C double bond of three substrates and even outperformed the natural coenzyme. Kinetic data are reported.