Molecular modeling studies of a parallel stranded quadruplexes containing a 8-bromoadenosine.
Truncated sequences of human telomeric DNA can readily assemble to form parallel stranded quadruplexes containing A- and G-tetrads. The formation of an A-tetrad is highly context-dependent and the relationship between the formation of an A-tetrad and the glycosidic torsion angle of the adenosine residues implicated has not been completely clarified so far. In order to give a further insight in this issue we synthesized the modified oligomers d(ABrGGGT) and d(TABrGGGT), two different truncations of the human telomeric sequence containing a 8-bromoadenosine residue, named ABr. NMR data show that both the modified oligomers are able to perfectly fold into highly symmetric quadruplexes with all strands parallel to each other. Molecular modeling studies were performed on both [d(ABrGGGT)]4 and [d(TABrGGGT)]4, indicating that a bulky substituent, such as a bromine atom at the C8 position of adenines, can force the glycosidic bond to adopt a syn conformation, stabilizing the resulting quadruplexes.
Esposito
Veronica
V
Dipartimento di Chimica delle Sostanze Naturali, Università degli Studi di Napoli Federico II, Napoli, Italy.
Randazzo
Antonio
A
Petraccone
Luigi
L
Giancola
Concetta
C
Erra
Eva
E
Virgilio
Antonella
A
Mayol
Luciano
L
D000241:Adenosine / Q000031:analogs & derivatives* / Q000737:chemistry; D006026:Glycoside Hydrolases / Q000737:chemistry; D006027:Glycosides / Q000737:chemistry; D006801:Humans; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D008958:Models, Molecular; D008967:Molecular Biology / Q000379:methods*; D008968:Molecular Conformation; D009690:Nucleic Acid Conformation; D009691:Nucleic Acid Denaturation; D016615:Telomere / Q000737:chemistry / Q000648:ultrastructure; D013696:Temperature
D006027:Glycosides; C036038:8-bromoadenosine; D006026:Glycoside Hydrolases; D000241:Adenosine