Pharmacophore Requirements for HIV-1 Reverse Transcriptase Inhibitors that Selectively “Freeze” the Pre-Translocated Complex During the Polymerization Catalytic Cycle

Publication date: Available online 14 February 2018
Source:Bioorganic & Medicinal Chemistry
Author(s): Cyrus M. Lacbay, Michael Menni, Jean A. Bernatchez, Matthias Götte, Youla S. Tsantrizos
Reverse transcriptase (RT) is responsible for replicating the HIV-1 genome and is a validated therapeutic target for the treatment of HIV infections. During each cycle of the RT-catalyzed DNA polymerization process, inorganic pyrophosphate is released as the by-product of nucleotide incorporation. Small molecules were identified that act as bioisosteres of pyrophosphate and can selectively freeze the catalytic cycle of HIV-1 RT at the pre-translocated stage of the DNA- or RNA-template-primer-enzyme complex.

Graphical abstract

http://ift.tt/2o8v82f