Linear Polymerization of a Synthetic Peptide of the V3 Region from HIV-1 JY1 Isolate Using Acetamidomethyl-protected Thiol Groups of Cysteine Residues

A method to carry out the linear polymerization of a synthetic peptide using acetamidomethyl (Acm)-protected thiol groups of cysteine residues, was developed. This polymer showed to be useful in the improvement of peptide immunogenicity. To achieve the polymerization, two Cys(Acm) residues were incorporated at both ends of the peptide. The model peptide contains B and T cell epitopes placed in tandem. The B cell epitope comprises 15 amino acids of the V3 region from HIV-1 JY1 isolate, and the helper T cell epitope belongs to the region 830–844 of the tetanus toxoid. The polymerization reaction consisted in an instant process of deprotection and oxidation of thiol groups at a high monomer concentration. This reaction proceeded quickly with about 80% of conversion. The monomer and the polymers were analyzed by gel filtration chromatography, reverse phase-high performance liquid chromatography, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and mass spectrometry. The sera obtained from mice immunized with the monomer and the polymer variants were assayed against a conjugated BSA-JY1 peptide in an indirect ELISA. The highest titer values corresponded to the polymer variant (p < 0.01). This result emphasizes that this strategy can be used to increase the immunogenicity of synthetic peptides in vaccines or therapeutics.