The bicyclams are a new class of anti-human @entity465 @entity778 targeted at viral entry. From marker rescue experiments, it appears that the envelope @entity7957 glycoprotein plays an important role in the anti-HIV activity of the bicyclams. @entity9019 -resistant strains contain a number of @entity535 changes scattered over the V2 to V5 region of @entity7957 . Experiments aimed at estimating the relative importance of particular @entity535 changes with regard to the overall resistance pattern are described. The sequences of some partially bicyclam-resistant virus strains, obtained during the resistance development process, were analyzed, and the corresponding 50% effective concentrations were determined. Selected mutations observed in @entity9019 -resistant strains were introduced in the wild-type background by site-directed mutagenesis. In addition, some @entity1522 were back-mutated to their wild-type counterparts in an otherwise @entity9019 -resistant strain. The sensitivities of these mutant viruses to bicyclams were determined. Construction of chimeric viruses, carrying the V3 loop of @entity9019 -resistant virus in a wild-type @entity16090 HXB2 background, enabled us to investigate the importance of the mutations in the V3 loop of @entity9019 -resistant virus. From the results described in the report, it can be concluded that single @entity535 substitutions do not influence the observed resistance to @entity9019 . Also, the mutations in the V3 loop are not sufficient to engender even a partially resistant phenotype. We postulate that the overall conformation of @entity7957 determines the degree of sensitivity or resistance of @entity645 strains to bicyclams.

Sensitivity of human @entity465 virus to bicyclam derivatives is influenced by the three-dimensional structure of XXXX .

@entity778 :: ('MESH:D015658', 'Disease') :: ['virus (anti-HIV) compounds'] @entity1522 :: ('CHEBI:33709', 'Chemical') :: ['amino acids'] @entity535 :: ('CHEBI:33704', 'Chemical') :: ['amino acid'] @entity645 :: ('57667', 'Species') :: ['HIV'] @entity7957 :: ('3700', 'Gene') :: ['gp120'] @entity465 :: ('MESH:D007153', 'Disease') :: ['immunodeficiency'] @entity9019 :: ('MESH:C088327', 'Chemical') :: ['JM3100', 'bicyclam', 'Bicyclam'] @entity16090 :: ('11709', 'Species') :: ['HIV type 1']
@entity7957 :: (3700,Gene) :: ['gp120']
