Substituted 1,8-Naphthyridin-2(1H)-ones Are Superior to Thymine in the Recognition of Adenine in Duplex as Well as Triplex Structures

Citations Over TimeTop 16% of 2002 papers

Abstract

The synthesis and evaluation of a series of novel nucleobases based on substituted 1,8-naphthyridin-2(1H)-ones are reported. The nucleobases were designed to meet the requirements for incorporation into peptide nucleic acids (PNAs) and were evaluated as part of PNA duplex and triplex nucleic acid recognition systems. Of the various nucleobases tested, only the 7-chloro-1,8-naphthyridin-2(1H)-one (7-Cl-bT) nucleobase led to consistently increased affinity in all recognition systems, duplex (Watson-Crick) as well as triplex (Hoogsteen). For multiply modified systems, the increase in thermal stability per modification was dependent on the sequence context, ranging from 2.0 degrees C (in separate positions) to 3.5 degrees C (in adjacent positions) in PNA-DNA duplexes and from 1.2 degrees C (in separate positions) to 3.2 degrees C (in adjacent positions) in PNA-RNA duplexes. Singly mismatched oligonucleotide targets were employed to demonstrate uncompromised sequence discrimination. When part of multiply modified triplex (Hoogsteen) recognition systems, the 7-Cl-bT unit gave rise to increases in the thermal stability ranging from 2.7 to 3.5 degrees C when incorporated into separated and adjacent positions, respectively. Our results furthermore indicate that the duplex stabilization is predominantly enthalpic and therefore most likely not a consequence of single-strand preorganization. Finally, and most surprisingly, we find no direct correlation between the end-stacking efficiency of this type of nucleobase and its helix stabilization when involved in Watson-Crick base pairing within a helix.

Related Papers

• → Strand Invasion of Mixed-Sequence, Double-Helical B-DNA by γ-Peptide Nucleic Acids Containing G-Clamp Nucleobases under Physiological Conditions(2011)58 cited
• → Hydrogen Bonding or Stacking Interactions in Differentiating Duplex Stability in Oligonucleotides Containing Synthetic Nucleoside Probes for Alkylated DNA(2013)24 cited
• → Hydrogen bonding versus stacking stabilization by modified nucleobases incorporated in PNA·DNA duplexes(2009)17 cited
• → Nucleic acid analog peptide (NAAP) 2. Syntheses and properties of novel DNA analog peptides containing nucleobase linked β-aminoalanine(1997)19 cited
• → Synthesis and duplex-forming ability of oligonucleotides modified with 4′-C,5′-C-methylene-bridged nucleic acid (4′,5′-BNA)(2021)2 cited