Peptide Paratope Mimics of the Broadly Neutralizing HIV-1 Antibody b12

Abstract The broadly neutralizing HIV‐1 antibody b12 recognizes the CD4 binding site of the HIV‐1 envelope glycoprotein gp120 and efficiently neutralizes HIV‐1 infections in vitro and in vivo. Based on the 3D structure of a b12 ⋅ gp120 complex, we have designed an assembled peptide (b12‐M) that presents the parts of the three heavy‐chain complementarity‐determining regions (CDRs) of b12, which contain the contact sites of the antibody for gp120. This b12‐mimetic peptide, as well as a truncated peptide presenting only two of the three heavy‐chain CDRs of b12, were shown to recognize gp120 in a similar manner to b12, as well as to inhibit HIV‐1 infection, demonstrating functional mimicry of b12 by the paratope mimetic peptides.