CLICK-CHEMISTRY BASED TWO-COMPONENT COVALENT INHIBITOR (TCCI) AGAINST HIV-RT

Carlos E. Ledezma and Dmitry M. Kolpashchikov

University of Central Florida

Current HIV-RT inhibitors are inherently promiscuous, cause numerous side-effects, and must be taken in conjunction with other drugs to prevent viral mutations. We demonstrate that two-component covalent inhibitors (TCCI’s) are an effective alternative to current nucleoside reverse transcriptase inhibitors (NRTI’s). Two click-reactive dTTP analogs were designed to inhibit HIV-RT where up to 87% inhibition is observed in the presence of both analogs, but the individual analogs show only light to moderate inhibition.