Immunogenicity of synthetic HIV-1 gp120 V3-loop peptide-conjugate immunogens.

A successful prophylactic human immunodeficiency virus type 1 (HIV-1) vaccine must elicit an immune response that will prevent establishment of the persistent viral infection. The only response shown to be effective in this regard is virus-neutralizing antibody directed against the viral gp120 hypervariable V3-loop region. Conjugate immunogens, containing cyclic peptides representing the V3 determinant covalently bound to a carrier protein, were capable of eliciting virus-neutralizing antibodies.

Identification of HIV vaccine candidate peptides by screening random phage epitope libraries.

Most synthetic HIV-1 gp120 V3 loop peptides that are used as immunogens in experimental HIV-1 vaccine studies are modeled from the naturally occurring viral gp120 V3 loops. In experimental animals these immunogens generally elicit type (or variant)-specific neutralizing antibodies that are not broadly reactive among HIV-1 variants. In an attempt to find a more general structure for the V3 loop, we have obtained candidates that mimic V3 loop sequences by screening random epitopes displayed in a fusion phage 15-residue epitope library.

Structure activity of C-terminal modified analogs of Ac-CCK-7.

Previous work indicates that both the C-terminal phenylalanine amide and the tryptophan moieties of cholecystokinin (CCK) are critical pharmacophores for interaction with either the A or B receptor subtypes. We have examined a series of analogs of Ac-CCK-7 [Ac-Tyr(SO3H)-Met-Gly-Trp-Met-Asp-Phe33-NH2] (2) in which the phenyl ring of the C-terminal Phe-NH2 has been modified. Compounds were assessed in binding assays using homogenated rat pancreatic membranes and bovine striatum as the source of CCK-A and CCK-B receptors respectively and for anorectic activity after intraperitoneal administration to rats.