Physico-chemical studies of quadruple helices of modified human telomeric DNA

The ends of chromosomes, termed telomeres, is composed of telomeric DNA and various telomere-associated proteins. Although most of telomeric DNA is double-stranded, the extreme 3'-end of the telomere consists of single-stranded G-rich DNA overhangs [1]. Human telomeric DNA contains tandem repeats of the sequence TTAGGG and the guanine-rich strand folds into an intramolecular quadruplex structure in Na+ solution. The structure of the telomeric DNA has been extensively studied in recent years due to the identification of a possible biological role and potential biotechnological and therapeutic applications. These structures seem to be involved in the recombination at G-rich sequences, telomere protection and elongation and transcriptional regulation [2]. The ability to chemically synthesize oligonucleotide analogues has opened up the opportunity to observe changes in their structures and activities that occur even upon single residue substitution [3]. The incorporation of modified bases into oligonucleotides may indeed produce useful changes in physical and biological properties of the resulting DNA fragments. In this work, the physico-chemical properties of quadruplex structures of the human telomeric repeat oligonucleotide d(TAGGGT), d(AGGGT) and modified sequences were compared. The adenine was substituted by 2'-deoxy-8-(propyn-1-yl)adenosine (AAPr) and by 8-bromodeoxyadenosine (A ABr).