Biophysical properties of quadruple helices of modified human telomeric DNA.
Telomeric DNA of a variety of vertebrates including humans contains the tandem repeat d(TTAGGG)n. The guanine rich strand can fold into four-stranded G-quadruplex structures, which have recently become attractive for biomedical research. Indeed, the aptamers based on the quadruplex motif may prove useful as tools aimed at binding and inhibiting particular proteins, catalyzing various biochemical reactions, or even serving as pharmaceutically active agents. The incorporation of modified bases into oligonucleotides can have profound effects on their folding and may produce useful changes in physical and biological properties of the resulting DNA fragments. In this work, the adenines of the human telomeric repeat oligonucleotide d(TAGGGT) and d(AGGGT) were substituted by 2'-deoxy-8-(propyn-1-yl)adenosine (A-->APr) or by 8-bromodeoxyadenosine (A-->ABr). The biophysical properties of the resulting quadruplex structures were compared with the unmodified quadruplexes. NMR and CD spectra of the studied sequences were characteristic of parallel-stranded, tetramolecular quadruplexes. The analysis of the equilibrium melting curves reveals that the modifications stabilize the quadruplex structure. The results are useful when considering the design of novel aptameric nucleic acids with diverse molecular recognition capabilities that would not be present using native RNA/DNA sequences.
Petraccone
Luigi
L
Dipartimento di Scienze Farmaceutiche, Via Ponte Don Melillo, 84084, Fisciano (SA), Italy.
Erra
Eva
E
Esposito
Veronica
V
Randazzo
Antonio
A
Galeone
Aldo
A
Barone
Guido
G
Giancola
Concetta
C
D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry*; D003839:Deoxyadenosines / Q000737:chemistry*; D054856:G-Quadruplexes; D006801:Humans; D019906:Nuclear Magnetic Resonance, Biomolecular; D009690:Nucleic Acid Conformation; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D020080:Tandem Repeat Sequences / Q000235:genetics; D016615:Telomere / Q000737:chemistry* / Q000235:genetics; D013816:Thermodynamics; D044366:Transition Temperature
C492377:2'-deoxy-8-(propyn-1-yl)adenosine; D003839:Deoxyadenosines; D009838:Oligodeoxyribonucleotides; C042464:8-bromo-2'-deoxyadenosine; D004247:DNA