Structural effect of synthetic zwitterionic cosolutes on the stability of DNA duplexes

The molecular design of useful cosolutes for polymerase chain reaction (PCR), which is one of the most important techniques in molecular biology, plays a significant role in amplification of highly stable genome sequences because during PCR, strand dissociation sometimes fails due to high melting temperature. Here, we designed and synthesized eight new zwitterionic cosolutes derived from glycine betaine, a destabilizing reagent for GC-rich DNA duplexes, and systematically compared their ability to destabilize DNA duplexes and to amplify genome DNA by PCR. We found that introduction of n-butyl groups rather than methyl groups into the ammonium group reduced the melting temperature of DNA duplexes 11-fold more than what was observed for the scaffold cosolute, glycine betaine, and furthermore, the cosolute can amplify the stable genome sequence by PCR.