Preparation of carboxythiolactones and their active derivatives

The design of peptidyl immunogens requires that a number of elements be cov alently linked to enable the appropriate immune response to occur. Two of t hese elements are: (a) T-cell sequences which after processing, bind to maj or histocompatibility complex (MHC) molecules and T-cell receptors and (b) B-cell sequences which embody the constellation of atoms which will ultimat ely be recognized by the desired antibody. Our concept, designed to effectu ate this, involved a single molecule which could conjugate three peptides, potentially in discrete steps, in one pot. Activated carboxythiolactones, h itherto unknown entities, provide such a system: two acyl sites susceptible to nucleophilic attack at disparate rates and a liberated thiol susceptibl e to electrophilic alkylation. Such a set of thiolactones and their derivat ives have been synthesized from inexpensive starting materials and their re activities are under investigation. If successful, the system will not only obviate the difficult syntheses of longer linear peptides, but will also a llow a rapid structural permutation of the various elements.