Melissa S. Egbertson

TL;DR: It is demonstrated that an acidic moiety such as a carboxylate or isosteric heterocycle is not required for binding to the enzyme complex but is essential for inhibition and confers distinct metal-dependent properties on the inhibitor.

TL;DR: These studies provide a structural basis and rationale for developing integrase inhibitors with the potential for unique and nonoverlapping resistance profiles and propose a model of the two inhibitors that is consistent with this observation and suggests specific interactions with discrete binding sites for each ligand.

TL;DR: A scintillation proximity assay is developed that permits analysis of radiolabeled inhibitor binding and integrase function and elucidate the basis for diketo acid inhibition of strand transfer and have implications for integrase-directed HIV-1 drug discovery efforts.

TL;DR: Naphthyridine 7 inhibits the strand transfer of the integration process catalyzed by integrase with an IC50 of 10 nM and inhibits 95% of the spread of HIV-1 infection in cell culture at 0.39 microM.