Zwitterionic DNA

• Published in: Journal of the American Chemical Society 1993-08, Vol.115 (16), p.7128-7134
• Main Authors: Hashimoto, Hiromasa, Nelson, Marek G, Switzer, Christopher
• Format: Article
• Language: English
• Subjects: Antineoplastic agents; Biological and medical sciences; General aspects; Medical sciences; Pharmacology. Drug treatments
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja00069a009

As a strategy to make DNA net charge neutral, oligodeoxynucleotides bearing pyrimidine 5- omega -aminohexyl substituents have been synthesized and characterized. The resultant zwitterionic oligomers bind to natural DNA at low ionic strength as well or better than does natural DNA with itself, even when all of the nucleotides in a given single strand are rendered zwitterionic. As would be expected, stabilities of duplexes bearing zwitterionic strands are relatively insensitive to changes in solution ionic strength as compared with natural DNA. Somewhat surprising, however, is the finding that a DNA duplex composed of a fully zwitterionic strand and a natural complementary strand exhibits no change in stability over a 20-fold change in ionic strength. Thus, double- and single-stranded states in this case have equivalent charge densities, consistent with the zwitterionic strand contributing no net charge. Stabilization due to the ammonium ions was verified by comparing free energies of DNA duplexes bearing hexyl tethered ammonium ions with those bearing simply hexyl groups devoid of ammonium ions. This comparison showed that without an added positive ammonium ion, the hexyl tether 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.