Fig. 1. (A) Top view of the structure of HIV-1 gp41 6-HB (PDB: 1AIK). (B) Strategy for the preparation of thioester-modified peptides. (C) Schematic representation of isopeptide bond formation via an inter-helical acyl transfer reaction. For clarity, only one of the three symmetrical active sites is shown. (D) The sequences of our designed N36 derivatives. The inter-helical i to i′ + 5 ionic interactions are shown in yellow. Isopeptide bonds are formed between Lys-6 and Glu-11 (in red). These peptides have an acetyl group at the N-terminus and carboxyamide at the C-terminus.