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Alpha-anomeric configuration of GT oligodeoxynucleotide leads to loss of the specific aptameric and cytotoxic properties retained by the beta-anomeric analog.

The development of antisense, antigene, or aptameric oligonucleotides to modulate in vivo cellular functions depends on using stable biologic molecules. Previous investigations showed that GT oligonucleotides could exert a specific, dose-dependent cytotoxic effect on human cancer cell lines. This is tightly related to the ability of these oligomers to specifically bind nuclear proteins, giving a complex of apparent molecular weight of 45 kDa. We demonstrated that with respect to the cytotoxic GT-beta-oligomer, alpha-anomeric GT analog did not alter the growth of the T lymphoblastic CCRF-CEM cell line, although the cells took it up efficiently. In agreement with this, GT-alpha-oligomer did not form the cytotoxicity-related 45-kDa complex with nuclear proteins. These findings likely could be related to the ability of GT-alpha to structure under nondenaturing conditions because of the high number of T in the sequence.