Design and synthesis of a biologically active antibody mimic based on an antibody-antigen crystal structure

Article abstract of DOI:10.1021/ja00086a005

We have used the crystal structure of an N9 sialidase (antigen)-NC41 (antibody) complex to design a low molecular weight compound that mimics the binding function of the macromolecular antibody. The components of recognition between the antibody and the protein antigen have been analyzed from the energy-refined crystal complex. From this analysis, four amino acid residues on the antibody binding surface, which make direct contact with the active-site loop 368-370 of the antigen, have been identified as contributing the majority of the binding energy of the protein. The designed target compound, a constrained cyclic peptide, which mimics the receptor-bound conformation of these amino acids, has been synthesized and found to inhibit N9 sialidase activity, with a K(i) of 1 x 10^-4 M.