| Structure aided design of HIV PR inhibitors has led to a class of drugs useful in clinical anti-HIV intervention. Nevertheless, mutational development of HIV PR drug resistance presents a major medical complication. Thus, the present state of anti-AIDS therapies calls for design of novel compounds that would overcome the problem of HIV PR resistance to the current drugs. Recently, a combinatorial chemistry approach yielded a series of novel pluripotent HIV PR inhibitors having a picomolar range of their Ki values for the wild-type HIV PR as well as various degree of insensitivity of their inhibitory potency to HIV PR mutations conferring Saquinavir, Ritonavir and Indinavir resistances. Detailed kinetic analysis of three chosen inhibitors has, in certain cases, shown even somewhat better inhibition of a drug-resistant HIV PR mutant in comparison to the wild-type enzyme. |
