This project covers the design, synthesis and use of new reagents and chemical constructs that will meet specific requirements in research projects of collaborating groups or individuals. Research goals fall within the fields of basic and applied immunology and structural biology. For the preparation of conjugates and immunoadsorbents, heteroligation strategies have played a central role in our work. In these strategies, two disparate structures are cross-linked without self-polymerization by placing uniquely interacting functions on each component through chemical derivatization. We have favored the use of sulfhydryl and sulfhydryl- selective groups as the paired functions, with cross-linking occurring through formation of stable thioether linkages. New reagents have been developed for the placement of sulfhydryl-selective, haloacetyl (chloro-, bromo- and iodoacetyl) groups onto proteins, peptides and polymers. A US patent was issued on the synthesis and use of a novel reagent for placing bromoacetyl group as a side chain at any desired position of a peptide being synthesized by solid-phase or other sequential methods. A new compound was designed and synthesized that serves as a lipid component in the preparation of liposomes and provides sulfhydryl- reactive iodoacetamido groups at their aqueous interfaces. Immunogenic liposomes were prepared by reacting the above material with synthetic peptide antigen epitopes containing a cysteine residue. Using peptides from the HIV-1 V3-loop, strongly immunogenic liposomes have been prepared that may serve as a prototype for an AIDS vaccine. The compound, a derivative of phosphatidylethanolamine, should be generally useful for incorporating biologically active peptides into liposome carrier constructs.
