ZWITTERIONIC DNA

As a strategy to make DNA net charge neutral, oligodeoxynucleotides be aring pyrimidine 5-omega-aminohexyl substituents have been synthesized and characterized. The resultant zwitterionic oligomers bind to natur al DNA at low ionic strength as well or better than does natural DNA w ith itself, even when all of the nucleotides in a given single. strand are rendered zwitterionic. As would be expected, stabilities of duple xes bearing zwitterionic strands are relatively insensitive to changes in solution ionic strength as compared with natural DNA. Somewhat sur prising, however, is the finding that a DNA duplex composed of a fully zwitterionic strand and a natural complementary strand exhibits no ch ange in stability over a 20-fold change in ionic strength. Thus, doubl e- and single-stranded states in this case have equivalent charge dens ities, consistent with the zwitterionic strand contributing no net cha rge. Stabilization due to the ammonium ions was verified by comparing free energies of DNA duplexes bearing hexyl tethered ammonium ions wit h those bearing simply hexyl groups devoid of ammonium ions. This comp arison showed that without an added positive ammonium ion, the hexyl t ether itself has a severe and cumulative unfavorable effect on duplex stability. Finally, zwitterionic nucleotides are found to distinguish matched from mismatched nucleotides in complementary DNA strands to a degree that rivals natural DNA.