Cyclic PNA hexamer-based compound: modelling, synthesis and inhibition of the HIV-1 RNA dimerization process

A cyclic molecule constituted by (i) a hexameric PNA moiety complementary to six among the nine residues of the dimerization initiation site loop of HIV-1 and (ii) a spacer tethering the N- to the C-extremities of the PNA, has been elaborated to inhibit the dimerization process of HIV-1 genome. This compound has been synthesized following a liquid-phase procedure (fully protected backbone approach). Preliminary agarose gel electrophoresis analyses have shown that the cyclic PNA conjugate is able to inhibit the HIV-1 dimerization. Graphic