PRODUCTION OF LINEAR-POLYMERS OF HIV GP120-BINDING DOMAINS

It has been demonstrated previously that molecular decoys of the acety lcholine 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 recombina nt linear polymers of the HIV gp120-binding domains which are situated within the T-cell membrane protein CD4. Whereas the production of lin ear concatemers of CD4 variable domains is feasible, a number of confo rmational constraints must be considered when designing a polymeric mo lecule which retains biological function. Most significant is the cont ribution of domains flanking the binding site that apparently enable c orrect folding of the latter.