This project focuses on the study of physico-chemical characteristics, and structural properties of proteins in order to elucidate different molecular forms and structural requirements for various biological activities. During this reporting period, a medicinal plant protein from the seeds and fruits of Momordica charantia, designated as MAP 30 or Momordica anti-human immunodeficiency virus (HIV) protein, was studied. This protein has been purified to homogeneity, is basic, 30 kDa in size, and exhibits dose-dependent inhibition of cell-free HIV-1 infection and replication. The sequence analysis of the amino-terminal 44 amino acid residues of MAP 30, and of the closely related and functionally similar medicinal plant proteins, trichosanthins, have revealed 34% and 57% sequence homology to ricin A chain and trichosanthin, respectively, when both identical and conserved residues are taken into account for comparison. Consistent with this finding, MAP also inhibits eukaryotic translation in vitro. However, unlike ricin and trichosanthin, this new protein is not toxic to intact host cells at the dose levels at which HIV infection and replication experiments were performed. Tricosanthins are now in the phase 2 clinical evaluation for the treatment of acquired immunodeficiency syndrome (AIDS). The available data suggest that MAP 30 may be a superior therapeutic agent in the treatment of HIV infections. For the future course of the project, complete primary protein structure will be elucidated and attempts will be made to understand secondary and tertiary structures that will be essential in the design of analogues and the understanding of structure-function relationships. Furthermore, target-oriented MAP-CD4 or MAP-antiCD4 antibody complexes will be prepared in order to increase the efficacy of the protein in the treatment of AIDS.
