Structural Studies on LNA Quadruplexes

LNAs (locked nucleic acids) are new DNA analogs with higher binding affinities toward nucleic acids than the canonical counterparts mainly due to the characteristic conformational restriction arising from the 2'-O, 4'-C methylene bridge. In light of the promising therapeutic applications and considering the advantageous characteristics of LNAs, such as their high water soly., easy handling, and synthetic accessibility through the conventional phosphoramidite chem., we undertook a study concerning the capability of these nucleic acid analogs to form quadruplex structures. Particularly, we have been investigating the LNA/DNA chimeras corresponding to the well-known DNA sequences 5'-GGTTGGTGTGGTTGG-3', capable of forming an unimol. quadruplex. This article deals with the study of the sequence 5'-ggTTggTGTggTTgg-3' (upper and lower case letters represent DNA and LNA residues, resp.), which, according to CD spectroscopy, is able to fold into a quadruplex structure.