A physico-chemical characterization, based on NMR and CD spectroscopy, of quadruplexes formed by the oligonucleotide d(TGGGT), where two or three Gs are substituted by 8-bromo-2′-deoxyguanosine residues (dG Br ), is reported. The oligonucleotidic sequences d(TG Br G Br GT), d(TG Br GG Br T), d(TGG Br G Br T), and d(TG Br G Br G Br T) have been synthesized. Only sequences d(TG Br GG Br T) and d(TG Br G Br GT) were able to fold into a well defined quadruplex structure, and their CD profiles and thermal stabilities turned out to be very different from those observed for the natural counterpart, indicating that the 8-Br-dG residues dramatically affect the structure of the quadruplex