Project C1: Jutta Eichler

Virology

Head of Institute:
Prof. Dr. med. Klaus Überla

Towards novel HIV immunotherapeutics: bispecific antibody paratope mimics

Utilizing our expertise in the design and generation of paratope mimetic peptides (Haußner et al., 2017a; Haußner et al., 2017b), the aim of this project is to generate synthetic bispecific antibody mimics that are able to simultaneously contact different, yet spatially adjacent epitopes on HIV-1 Env (Fig. 1). The project will involve the generation, through solid-phase peptide synthesis, of antibody paratope mimetic peptides, including the purification (preparative HPLC) and analysis (LC-MS) of the synthesized peptides, as well as the fusion of two such peptides through chemo-selective ligation reactions. The interaction of the synthesized peptides with HIV-1 Env proteins (gp120 and gp41) will be analyzed using a range of methods, including SPR spectroscopy, fluorescence polarization and ELISA. This project will be conducted in close collaboration with virology (C5) and bioinformatics (C2) partners.

Figure 1. Simultaneous interaction of bispecific antibody paratope mimetic peptides presenting CDRs (shown in yellow, green and red) of different antibodies that recognize spatially adjacent epitopes on the same protein (gp120, right), or on two separate proteins (gp120 and gp41, left).