Betaine structure and the presence of hydroxyl groups alters the effects on DNA melting temperatures

Betaine lowers the melting temperature of deoxyribonucleic acid (DNA) and decreases its dependence on base composition. The effects of synthetic betaine analogs on the melting of DNA samples with different GC content were measured. Since many polyhydroxy compounds also lower DNA melting temperatures, hydroxyl‐substituted betaine analogs were included. Some synthetic sulfonate analogs of betaine lowered the DNA melting temperatures by twice as much at the same molar concentration. They were up to twice as effective at decreasing the base pair dependence. Some carboxylate homologs of betaine, substituted with hydroxyl groups, increased the melting temperature. This effect was greater with low GC content DNA. Sulfonate analogs of betaine with hydroxyl groups usually destabilize the DNA, while their carboxylate analogs stabilize the DNA. Distances between the charges of these synthetic zwitterionic solutes influence the effect on DNA, with the optimum separation being two or three methylene groups. A betaine with two hydroxyl groups on one N‐alkyl group had a greater effect than an isomer with two hydroxyl groups on separate N‐alkyl substituents. We suggest that the effect of these solutes depends on structuring the hydration water of DNA, as well as interactions with the DNA structure itself. © 2008 Wiley Periodicals, Inc. Biopolymers 91: 85–94, 2009. This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com