Design of an artificial molecular catalyst showing peptidase activity to the conserved sequence of HIV-1 envelope gp41

In designing the molecular catalyst having the ability to decompose the target molecule, two kinds of antigen recognition sites of the monoclonal antibodies were employed. One is anti-glycoprotein (gp) 41 monoclonal antibody raised against the highly conserved sequence (RGPDRPEGIEEEGGERDRD) of human immunodeficiency virus (HIV)-1 envelope. The conserved sequence is the molecule targeted in this study. Another is anti-hemin monoclonal antibody (1D3 antibody) which can firmly bind with porphine molecule. In these two monoclonal antibodies, the 16 mer peptide of the complementarity determining region (CDR)-1 in the light chain of the anti-gp41 monoclonal antibody displayed the strong binding affinity to the above targeted peptide molecule. As 17 mer peptide of the CDR-2 in the heavy chain of the 1D3 antibody had a strong interaction with porphyrin. The above 16 and 17 mer peptides were bridged via a spacer of -Gly-Pro-. The synthesized polypeptide could simultaneously uptake both porphyrin and targeted peptide. In addition, the polypeptide accelerated the decomposition of the targeted peptide by 6-14 fold, showing the peptidase activity as an artificial catalyst. (C) 2000 Elsevier Science B.V. All rights reserved.