The effects of post-translational side-chain modifications on the stimulatory activity, serum stability and conformation of synthetic peptides carrying T helper cell epitopes

摘要: Abstract Peptides 31D and VF 13, corresponding to the rabies virus nucleo- glycoproteins, respectively, vigorously stimulate T helper cells of appropriate specificity. Earlier we showed how internal external glycosylation affects major histocompatibility complex molecule (MHC)-binding ability conformation these T-cell epitopes (Otvos et al. (1994) Biochim. Biophys. Acta 1224, 68–76; Otvos (1995) 1267, 55–64). In current report, examined T-helper cell stimulatory after introduction a new set post-translational modifications. To obtain general information concerning effects amino acid side-chain modifications on other biochemical properties protein fragments, studied serum stability VF13 peptides. We found that extent reduction activity depends upon location in sequence host residue. Generally, (β-linked sugars mid-chain positions had greater inhibitory effect than a-linked attached identical acids. case where just marginally reduced activity, β-linked glycopeptide was significantly more resistant proteases. This finding suggests addition carbohydrates might be superior for vaccine development, generally peptide agonist drug design. addition, data presented here provide first documentation phosphorylation sulfation tyrosine residues may retain MHC-binding class II epitopes. The sulfated phosphorylated peptides exhibited considerably increased compared unmodified parent peptide. Finally, all destabilized dominant α-helical or turn structures aqueous trifluoroethanol mixtures. While circular dichroism spectra α- glycopeptides with monosaccharides were almost indistinguishable, structure depended length sugar moiety. Significantly, incorporation sulfate phosphate groups resulted conformations.