Effect of Ethylene Glycol, Urea, and N-Methylated Glycines on DNA Thermal Stability: The Role of DNA Base Pair Composition and Hydration

Publisher Website
Google Scholar
Abstract
The accumulation of the cosolutes ethylene glycol, urea, glycine, sarcosine, and glycine betaine at the single-stranded DNA surface exposed upon melting the double helix has been quantified for DNA samples of different guanine−cytosine (GC) content using the local-bulk partitioning model [Record, M. T., Jr., Zhang, W., and Anderson, C. F. (1998) Adv. Protein Chem. 51, 281−353]. Urea and ethylene glycol are both locally accumulated at single-stranded DNA relative to bulk solution. Urea exhibits a stronger affinity for adenine (A) and thymine (T) bases, leading to a greater net dehydration of these bases upon DNA melting; ethylene glycol local accumulation is practically independent of base composition. However, glycine, sarcosine, and glycine betaine are not necessarily locally accumulated at single strands after melting relative to bulk solution, although they are locally accumulated relative to double-stranded DNA. The local accumulation of glycine, sarcosine, and glycine betaine at single strands relative to double-stranded DNA decreases with bulk cosolute molality and increases with GC content for all N-methylated glycines, demonstrating a stronger affinity for G and C bases. Glycine also shows a minimum in melting temperature Tm at 1−2 m for DNA samples of 50% GC content or less. Increasing ionic strength attenuates the local accumulation of urea, glycine, sarcosine, and glycine betaine and removes the minimum in Tm with glycine. This attenuation in local accumulation results in counterion release during the melting transition that is dependent on water activity and, hence, cosolute molality.