Scheme 1. Design of Click-Chemistry-Based Two-Component Inhibitor (TCI) for Inactivation of HIV RT.

(A) HIV RT-assisted Cu-free “click” reaction and possible HIV RT inhibition. In vivo R1 and R2 could be the residues of NRTI triphosphates or viral RNA/DNA. In this work, R1 and R2 were a dTTP analogue and a DNA primer/template, respectively. (B) Synthetic schemes for 6Az-dTTP and DBCO-dTTP starting from aadTTP. The yields were 31 and 19% for 6Az-dTTP and DBCO-dTTP, respectively. (C) Primer/template (P/T) design for “click” chemistry-based TCI. The primer was fluorescein (FAM) labeled. The protruding 3′ end of the template had only one A (red).