Umass Madical School
Drug resistance is one of the major causes for HIV-infected patients to lose lives. An innovative HIV-1 protease inhibitor scaffold needs to be developed to resolve drug resistance issues. During this investigation, HIV-1 protease inhibitors based on a novel keto-hydroxyethylene core were designed and synthesized based on the substrate envelope theory. This core targets to overcome drug resistance to Amprenavir and Darunavir caused by I50V mutation in the protease. The results of florescence resonance energy transfer (FRET) assays indicate that the new inhibitor has moderate enzymatic inhibitory activities against HIV-1 protease. In the future, a variety of drug analogues will be developed based on this new core structure and might provide better therapies against drug-resistant HIV-1.
Worcester Polytechnic Institute
Major Qualifying Project
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Chemistry and Biochemistry