2‐Methoxypyridine as a Thymidine Mimic in Watson–Crick Base Pairs of DNA and PNA: Synthesis, Thermal Stability, and NMR Structural Studies. (26th September 2017)

• Record Type: Journal Article
• Authors: Novosjolova, Irina; Kennedy, Scott D.; Rozners, Eriks
• Is Part Of: Chembiochem. Volume 18:Number 21(2017)
• Page Start: 2165
• Page End: 2170
• Publication Date: 2017-09-26
• Subjects: cationic base pairs -- DNA duplexes -- modified nucleobases -- peptide nucleic acids -- unnatural base pairs; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1002/cbic.201700400
• Languages: English
• ISSNs: 1439-4227

Abstract

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. Abstract : A positive contribution : Thermodynamic and NMR structural studies show that 2‐aminopyridine forms a protonated base pair with adenosine at pH 4.3. The work demonstrates the feasibility of using cationic unnatural base pairs for molecular recognition in fundamental research and practical applications.