Models of analogues 7 (cyan) and 9 (magenta) bound to K103N/Y181C RT. (A) Overlay of the two compounds as modeled in the binding pocket of K103N/Y181C HIV-1 RT. (B) The exocyclic amine in 9 cannot H-bond with the backbone NH of K101, as seen in crystal structures of 1. The N3 and linker NH both bind a water molecule that forms a bridge to the backbone carbonyl of E138. (C) The H-bonds with the backbone of K101 are restored in 7. In addition, the exocyclic amine and linker NH both H-bond a water molecule in a different orientation than is seen with 9.