Starting from peptides that are often identified from protein-protein interactions as binding entities, we characterize these weekly binding peptides and their binding epitope by STD NMR and then modify the affinity of these peptides by elaborate synthesis and computer modeling cycles. Repeated refinement of these structures can lead to an improvement of binding constants by a factor of more than 10,000. We have obtained very successfully compounds that block the CD4 receptor on human cells and are continuing the project towards more generalized enzyme-ligand interactions.
Rational optimization of the binding affinity of CD4 targeting peptidomimetics with potential anti HIV activity. Neffe AT, Bilang M, Grüneberg I, Meyer B.,
J. Med. Chem. 50, 3482-8, (2007).
Synthesis and optimization of peptidomimetics as HIV entry inhibitors against the receptor protein CD4 using STD NMR and ligand docking. Neffe AT, Bilang M, Meyer B., Org Biomol Chem. 4, 3259-67, (2006).
Synthesis of Neu5Ac oligosaccharides and analogues by transglycosylation and their binding properties as ligands to MAG. Neubacher B, Scheid S, Kelm S, Frasch AC, Meyer B, Thiem J.
ChemBioBhem. 7, 896-9 (2006).
A New Peptidomimetic HIV Entry Inhibitor Directed Against the CD4 Binding Site for the Viral GP120,
Axel T. Neffe & Bernd Meyer,
Angew. Chem.116, 2997 – 3000 (2004).