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Chembiochem. 2017 Nov 2;18(21):2165-2170. doi: 10.1002/cbic.201700400. Epub 2017 Sep 26.

2-Methoxypyridine as a Thymidine Mimic in Watson-Crick Base Pairs of DNA and PNA: Synthesis, Thermal Stability, and NMR Structural Studies.

Author information

1
Department of Chemistry, Binghamton University, The State University of New York, Binghamton, NY, 13902, USA.
2
Department of Biochemistry and Biophysics, University of Rochester School of Medicine and Dentistry, Rochester, NY, 14642, USA.

Abstract

The development of nucleic acid base-pair analogues that use new modes of molecular recognition is important both for fundamental research and practical applications. The goal of this study was to evaluate 2-methoxypyridine as a cationic thymidine mimic in the A-T base pair. The hypothesis was that including protonation in the Watson-Crick base pairing scheme would enhance the thermal stability of the DNA double helix without compromising the sequence selectivity. DNA and peptide nucleic acid (PNA) sequences containing the new 2-methoxypyridine nucleobase (P) were synthesized and studied by using UV thermal melting and NMR spectroscopy. Introduction of P nucleobase caused a loss of thermal stability of ≈10 °C in DNA-DNA duplexes and ≈20 °C in PNA-DNA duplexes over a range of mildly acidic to neutral pH. Despite the decrease in thermal stability, the NMR structural studies showed that P-A formed the expected protonated base pair at pH 4.3. Our study demonstrates the feasibility of cationic unnatural base pairs; however, future optimization of such analogues will be required.

KEYWORDS:

DNA duplexes; cationic base pairs; modified nucleobases; peptide nucleic acids; unnatural base pairs

PMID:
28858428
PMCID:
PMC5920655
DOI:
10.1002/cbic.201700400
[Indexed for MEDLINE]
Free PMC Article

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