Nucleic Acid Stability in Glycine Betaine Solutions: Correlating Small Molecule Interactions with Nucleic Acid Surfaces

Abstract

This work seeks to elucidate the mechanism of glycine betaine destabilization of DNA and RNA secondary structures to enhance our understanding of the physical chemistry of folded nucleic acids. Vapor pressure osmometry was used to quantify glycine betaine exclusion from nucleoside 5′-monophosphates (5′-NMPs). The majority of the exclusion was attributed to glycine betaine exclusion from anionic oxygens on the phosphate group and aliphatic carbons and oxygens on the sugar group. Glycine betaine was proposed to accumulate at the nucleobases with the greatest accumulation around guanine. Thermal denaturation transition temperatures of GC-rich DNA and RNA duplexes decrease to a greater extent with increasing glycine betaine concentration than AT- (adenine-thymine) and AU- (adenine-uracil) rich double helices. We propose favorable interactions between glycine betaine and amino groups exposed during unfolding account for the greater destabilization of GC-rich DNA and RNA.