Cyclic V3-loop-related HIV-1 conjugate vaccines. Synthesis, conformation and immunological properties.

Important note: Information in this article was accurate in 1993. The state of the art may have changed since the publication date.

Cyclic V3-loop-related HIV-1 conjugate vaccines. Synthesis, conformation and immunological properties.

Int J Pept Protein Res. 1993 May;41(5):455-66. Unique Identifier : AIDSLINE MED/93307860
Tolman RL; Bednarek MA; Johnson BA; Leanza WJ; Marburg S; Underwood DJ; Emini EA; Conley AJ; Merck Research Laboratories, Rahway, New Jersey.

Abstract: Branched undecapeptides with sequences related to the virus glycoprotein V3 domain sequences of the MN and IIIB variants of HIV-1 were synthesized and cyclized with a peptide (amide) closure to cyclic decapeptides. Two-dimensional NMR studies allowed protons for the MN variant-related cycle (L-697,250) to be assigned. Molecular modelling with distance geometry methods permitted a conformation to be identified which showed good agreement with ROESY and 2D NMR study data. A molecular dynamics simulation showed that the highly conserved loop tip sequence (Gly-Pro-Gly-Arg) was in a conventional beta-turn less than 50% of the time. For evaluation of immunogenicity and antibody characterization studies, covalent carrier conjugates were prepared. 3-Maleimidopropionylation of the Nle amino group of the cyclic peptides gave an electrophilic tether which captured a thiol group from a thiolated carrier protein, OMPC (outer membrane protein complex of Neisseria meningitidis). Through the use of a novel co-conjugation procedure, soluble immunogen-carrier molecules were prepared which had suitable physical properties for use as a vaccine. These V3-loop-based vaccines could elicit neutralizing antibody, but not consistently in all animals. Characterization of sera showed that responses were broadly virus neutralizing.

Keywords: Amino Acid Sequence Animal Antibody Formation AIDS Vaccines/*IMMUNOLOGY HIV Envelope Protein gp120/*IMMUNOLOGY HIV-1/*IMMUNOLOGY Molecular Sequence Data Neutralization Tests Peptide Fragments/CHEMICAL SYNTHESIS/*IMMUNOLOGY Rabbits Vaccines, Synthetic/*IMMUNOLOGY JOURNAL ARTICLE
931030
M93A0706

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