Quadruplexes of Human Telomere DNA Analogs Designed to Contain G:A:G:A, G:G:A:A, and A:A:A:A Tetrads

Abstrakt

Replacement of two to four guanines by adenines in the human telomere DNA repeat dG(3)(TTAG(3))(3) did not hinder the formation of quadruplexes if the substitutions took place in the terminal tetrad bridged by the diagonal loop of the intramolecular antiparallel three-tetrad scaffold, as proved by CD and PAGE in both Na+ and K+ solutions. Thermodynamic data showed that, in Na+ solution, the dG(3)(TTAG(3))(3) quadruplex was destabilized, the least by the two G:A:G:A tetrads, the most by the G:G:A:A tetrad in which the adenosines replaced syn-guanosines. In physiological K+ solution, the highest destabilization was caused by the 4A tetrad. In K+, only the unmodified dG(3)(TTAG(3))(3) quadruplex rearranged into a K+-dependent quadruplex form, none of the multiple adenine-modified structures did so. This may imply biological consequences for non repaired A-for-G mutations. (C) 2010 Wiley Periodicals, Inc. Biopolymers 93: 880-886, 2010.