A NEW APPROACH FOR AN HIV DOCKING-INHIBITOR DRUG DESIGNED ON THE BASIS OF THE DUAL RECOGNITION BINDING HYPOTHESIS BETWEEN THE CD4 RECEPTOR AND THE ENVELOPE GLYCOPROTEIN OF THE HIV

A structural hypothesis is presented in this paper for dual binding si tes between the gp120 of HIV and the T-cell. One of the binding sites involved electrostatic attraction between positively charged sites (Ly s(35), Lys(46) and Arg(59)) of the CD4 and the negatively charged site s (Asp(368), Glu(370) and Asp(457)) Of the gp120. It is suggested that the benzene ring of Phe(43) also acts as a lock at this site. The oth er site involves the galactose ending of one of the oligosaccharide an tennas of the CD4 that docks close to one of the S-S linkages (perhaps at Cys(296)-S-S-Cys(331)) Of the gp120. It is suggested that the acti vated free OH at C4 position of the galactose acts as a nucleophile to break this strategically located S-S linkage. Such a structural alter ation leads to a dramatic conformational change that may in fact trigg er the fusion process. On the basis of this structural hypothesis a ge neral glycopeptide structure is proposed that could act as a ''bivalen t'' docking-inhibitor drug.