HIV-1 ASPARTYL PROTEINASE RADIOPEPTIDASE ASSAY

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As an aid in the search for effective drugs against the HIV-1 virus that causes AIDS, a convenient radiopeptidase assay is proposed to be used in the screening for inhibitors of this enzyme responsible for infectivity. The HIV-1 aspartyl proteinase, one of the 3 functional enzymes of the retrovirus, clips the translated gag-pol polypeptide (viral gene product) into the mature virions in the infected cell. Inhibition of this enzyme prevents the cellular multiplication of infected virions. A sensitive biochemical assay for this enzyme is designed using a radiolabeled substrate that when cleaved by the aspartyl proteinase generates a labeled peptide fragment that is easily counted in solution. We propose to establish and optimize the assay, as well as to start screening for inhibitors.