Professor of Medicinal Chemistry
Friedrich Alexander University
Antibody Paratope Mimetic Peptides
The design of synthetic antibody paratope mimics presenting one or more of the antibody’s complementarity determining regions, CDRs, is a promising strategy to preserve antibody binding specificity in smaller molecules.
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 that presents the three heavy chain 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, as well as inhibit HIV-1 infection, in a b12-related fashion, demon-strating a functional mimicry of b12 by the paratope mimetic peptides.