Production of linear polymers of HIV gp120-binding domains.

It has been demonstrated previously that molecular decoys of the acetylcholine receptor have therapeutic efficacy as antitoxins [Gershoni, J. and Aronheim, A. (1988) Proc. Natl Acad. Sci. USA, 85, 4087-4089], but surely a most challenging goal is to apply this approach towards the development of antiviral drugs. As viruses present multiple copies of their envelope proteins, it was proposed that polyvalent decoys could be advantageous. Here we report the design and expression of recombinant linear polymers of the HIV gp120-binding domains which are situated within the T-cell membrane protein CD4. Whereas the production of linear concatemers of CD4 variable domains is feasible, a number of conformational constraints must be considered when designing a polymeric molecule which retains biological function. Most significant is the contribution of domains flanking the binding site that apparently enable correct folding of the latter.