Nicotinamide cofactor analogues

Nicotinamide cofactor analogues (mNADs), also called nicotinamide coenzyme biomimetics (NCBs), are artificial compounds that mimic the natural nicotinamide adenine dinucleotide cofactors in structure, to explore a mechanism or be used in biocatalysis or other applications.^[1] These nicotinamide cofactor mimics generally retain the nicotinamide moiety with varying substituents.

Background

An estimated 50% of oxidoreductases catalyze the transfer of a hydride using the nicotinamide adenine dinucleotide cofactor NAD(P).^[2] Nicotinamide adenine dinucleotide phosphate (NADPH) is used in anabolic reactions while nicotinamide adenine dinucleotide (NAD) is used in catabolic reactions.^[3] In the field of biocatalysis, NAD(P)-dependent oxidoreductases are widely used for the production of chiral alcohols, amines, and other valuable compounds. Yet the reduced forms of the cofactor, NADH and NADPH, needed for the catalysis, is too expensive to be used in stoichiometric amounts. Therefore a cofactor recycling system is usually employed.

Analogues

Nicotinamide cofactor analogues have been synthesized with varying substituents on the dihydropyridine ring to tune their redox potential and stability, to replace NADH or NADPH in certain enzymatic reactions. These synthetic cofactors have been used as early as 1937 to better understand the mechanisms of enzymatic reactions, in particular of alcohol dehydrogenases. These cofactor analogues can serve as an alternative to traditional cofactor regeneration techniques and be used in orthogol pathways.^[3][4]

References

1. "Is Simpler Better? Synthetic Nicotinamide Cofactor Analogues for Redox Chemistry", Caroline E. Paul, Isabel W. C. E. Arends, Frank Hollmann, ACS Catal. 2014, 4, 788-797
2. Sellés Vidal, Lara; Kelly, Ciarán L.; Mordaka, Paweł M.; Heap, John T. (February 2018). "Review of NAD(P)H-dependent oxidoreductases: Properties, engineering and application". Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics. 1866 (2): 327–347. doi:10.1016/j.bbapap.2017.11.005. hdl:10044/1/53944. PMID 29129662. S2CID 205856516.
3. Paul, Caroline E.; Arends, Isabel W. C. E.; Hollmann, Frank (2014-03-07). "Is Simpler Better? Synthetic Nicotinamide Cofactor Analogues for Redox Chemistry". ACS Catalysis. 4 (3): 788–797. doi:10.1021/cs4011056. ISSN 2155-5435.
4. Zachos, Ioannis; Döring, Manuel; Tafertshofer, Georg; Simon, Robert C.; Sieber, Volker (2021-06-21). "carba Nicotinamide Adenine Dinucleotide Phosphate: Robust Cofactor for Redox Biocatalysis". Angewandte Chemie International Edition. 60 (26): 14701–14706. doi:10.1002/anie.202017027. ISSN 1433-7851. PMC 8252718. PMID 33719153.