Synthesis of an oligonucleotide with a nicotinamide mononucleotide residue and its molecular recognition in DNA helices

• Published in: Organic & biomolecular chemistry 2015-01, Vol.13 (41), p.10303-10309
• Main Authors: Göckel, A, Richert, C
• Format: Article
• Language: English
• Subjects: DNA - chemistry; Molecular Conformation; Nicotinamide Mononucleotide - chemistry; Oligonucleotides - chemical synthesis; Oligonucleotides - chemistry
• ISSN: 1477-0520; 1477-0539
• DOI: 10.1039/c5ob01714a

Nicotinamide adenine dinucleotide (NAD) is a pivotal redox cofactor of primary metabolism. Its redox reactivity is based on the nicotinamide mononucleotide (NMN) moiety. We investigated whether NMN(+) can engage in pairing interactions, when incorporated into an oligonucleotide. Here we describe the incorporation of NMN(+) at the 3'-terminus of an oligodeoxynucleotide via a phosphoramidate coupling in solution. The stability of duplexes and triplexes with the NMN(+)-containing strand was measured in UV-melting curves. While the melting points of duplexes with different bases facing the nicotinamide were similar, triplex stabilities varied greatly between different base combinations, suggesting specific pairing. The most stable triplexes were found when a guanine and an adenine were facing the NMN(+) residue. Their triplex melting points were higher than those of the corresponding triplexes with a thymidine residue at the same position. These results show that NMN(+) residues can be recognized selectively in DNA helices and are thus compatible with the molecular recognition in nucleic acids.