Reduction of interstrand charge repulsion of DNA duplexes by salts and by neutral phosphotriesters – Contrary effects for harnessing duplex formation

Tai Chih Kuo, Meng Wei Wu, Wei Chen Lin, Daumantas Matulis, Yuh Shyong Yang, Si Yu Li, Wen Yih Chen*

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

To exploit the formation of DNA duplexes, the charge repulsion between complementary DNA strands can be reduced by adding salts or by replacing the negatively charged natural phosphodiester linkage(s) with charge-neutral methyl phosphotriester(s) (MPTE) linkage(s) of the synthetic nDNA oligonucleotides. Recently, we reported prominent improvements of detecting target nucleic acids with nDNA probes on liquid-phase PCR and solid/liquid-interface biosensing. To understand the observed improvements from thermodynamics perspectives, we studied the formation and stability of the double-stranded DNA (dsDNA) containing nDNA and/or natural DNA. With the natural DNA oligonucleotides, increment of Na+ cations caused unexpected reductions of favorable enthaply (ΔH) of duplex formation and expected increases of favorable free energy (ΔG) and temperature of melting transition (Tm). With one nDNA in duplex formation, the increase of Na+ yielded extra faborable ΔH, yet unfavorable ΔG and Tm. Possibly, Na+ cations (> 50 mM) promote the formation of dsDNA through the endothermic release of DNA (and nDNA)-hydrating water molecules more than through the reduction of inter-strand repulsions. The methyl groups of MPTE of nDNA also destabilize the DNA duplexes by hindering the formation of standard double helices. These novel findings explain the duplex-destabilization property of nDNA which enables its discrimination of single-nucleotide polymorphisms.

Original languageEnglish
JournalJournal of the Taiwan Institute of Chemical Engineers
DOIs
StateAccepted/In press - 1 Jan 2020

Keywords

  • DNA-hydrating water
  • Interstrand charge repulsion
  • Isothermal titration calorimetry
  • Methyl-phosphotriester DNA oligonucleotides

Fingerprint Dive into the research topics of 'Reduction of interstrand charge repulsion of DNA duplexes by salts and by neutral phosphotriesters – Contrary effects for harnessing duplex formation'. Together they form a unique fingerprint.

  • Cite this