Complexation of antiretroviral nucleosides 2 ',3 '-dideoxyinosine, 2 ',3 '-dideoxyadenosine and 2 ',3 '-dideoxygnanosine with beta-cyclodextrin. A H-1 NMR study

A number of successful applications have been found that use cyclodextrin c omplexation ability. In the present work we analyse beta-cyclodextrin (beta -CD) complexes with 2',3'-dideoxynucleosides (ddA, ddG, ddI) exhibiting hig h antiviral activity against HIV strains. The formation of the complexes ha s been analysed by H-1 NMR-monitored titration. On the basis of concentrati on dependencies of proton chemical shifts, the nucleosides in this study fo rm complexes of 1 : 1 stoichiometry with beta-CD. The bonding constants dep end on ligand type and could be estimated as 35 +/- 10 M-1 for ddA: 55 +/- 10 M-1 for ddI and 85 +/- 20 M-1 for ddG-beta-CD complexes. ROESY spectra d emonstrate that ligands penetrate the hydrophobic cavity of the beta-CD. Fi nally, on the basis of ROESY data, the "low resolution" ddG-beta-CD complex structure has been determined by multistep restrained molecular dynamics c alculations. Calculated ddG-beta-CD complex structure fully agrees with exp erimental data obtained for other beta-CD complexes.