[Biosensor analysis of interaction of potential dimerization inhibitors with HIV-1 protease]

Currently inhibitors of protein-protein interactions are considered as perspective prototypes of new generation of drugs. The most attractive targets for such inhibitors are the oligomeric enzymes which active sites are formed by amino acid residues from different subunits. The classic example of such enzyme is HIV protease (HIVp), active only in the homodimeric form. We have developed a new approach for experimental screening of HIVp dimerization inhibitors. It is based on the original biosensoric test-system for differential analysis of interaction of tested substances with HIVp dimers and monomers. Using this test-system we have analyzed the most perspective candidate substances predicted by method of virtual screening, and some derivatives of glycyrrhizin, triterpenic and steroid glycosides. As a result we found one compound, which mainly interacts with HIVp monomers and inhibits in vitro activity of this enzyme with IC50 of about 10(-6) M.