Anti-HIV-1 activity of an antisense phosphorothioate oligonucleotide bearing imidazole and primary amine groups

We have previously shown that RNA cleaving reagents with imidazole and prim ary amine groups on the 5 ' -end of antisense oligodeoxyribonucleotides cou ld site-specifically cleave CpA as the target sequence of the substrate tRN A in vitro. In this study, a RNA cleaving reagent, composed of imidazole an d primary amine groups on an antisense phosphorothioate oligonucleotide (Im -anti-s-ODN), was synthesized and evaluated for anti-HIV-1 activity in MT-4 cells. The sequence of the Im-anti-s-ODN was designed to be complementary to the HIV-1 gag-mRNA and to bind adjacent to the CpA cleavage site positio n. Im-anti-s-ODN encapsulated with the transfection reagent, DMRIE-C (R), h ad higher anti-HIV-1 activity than the unmodified antisense phosphorothioat e oligonucleotide (anti-s-ODN) at a 2 muM concentration. Furthermore, the I m-anti-ODN encapsulated with DMRIE-C (R) conferred sequence-specific inhibi tion. (C) 2001 Elsevier Science Ltd. All rights reserved.