PROLINE-RICH TANDEM REPEATS OF ANTIBODY COMPLEMENTARITY-DETERMINING REGIONS BIND AND NEUTRALIZE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 PARTICLES

The proline-rich tandem repeat domain of human mucin MUC1 forms an ext ended structure containing large repeating loops that are crested by a turn, We show that the repeating-loop structure of MUC1 can be replac ed by an antibody complementarity-determining region loop of a human i mmunodeficiency virus type 1 (HIV-1)-specific neutralizing antibody to create a chimeric, multivalent, mucin-like, anti-HN-l compound, We us ed 8 residues of an antibody molecule to replace 8 of 20 residues of t he MUC1 tandem-repeat sequence, The antiviral peptide discussed here c ontains three copies of a 20-residue tandem repeat, (IYYDYEEDPAPGSTA P PAHG)(3), for a total of 60 residues. We demonstrate that the mucin-an tibody chimera retains the binding specificity of the parent antibody (monoclonal antibody F58), GPGR of the HIV-1 gp120 V3 neutralizing epi tope, and the ability to neutralize virus particles, In inhibition enz yme-linked immunosorbent assay, the mucin-antibody chimeric peptide co uld inhibit. 71 to 84% of binding to a V3 loop peptide by monoclonal a ntibodies known to be specific for GPGR in the V3 loop, The mucin-anti body chimeric peptide could also inhibit monoclonal antibody binding t o native gp120 captured from virus particles, In addition, the chimeri c peptide neutralized the homologous HIV-IIIB virus in a standard neut ralization assay. The methods of antiviral peptide design and construc tion presented here are general and theoretically limited only by the size of the antibody repertoire. This approach could be used to synthe size peptides for a variety of therapeutic applications.