Influence of sequential oligopeptide carriers on the bioactive structure of conjugated epitopes: Comparative study of the conformation of a herpes simplex virus glycoprotein gD-1 epitope in the free and conjugated form, and protein "built-in" crystal structure

Dimitrios Krikorian, Athanassios Stavrakoudis, Nikolaos Biris, Constantinos Sakarellos, David Andreu, Eliandre De Oliveira, Gábor Mezö, Zsuzsa Majer, Ferenc Hudecz, Sytske Welling-Wester, Manh Thong Cung, Vassilios Tsikaris

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Synthetic carriers play an important role in immunogen presentation, due to their ability of inducing improved and specific responses to conjugated epitopes. Their influence on the bioactive conformation of the epitope, though admittedly crucial for relevant in vitro and in vivo applications, is difficult to evaluate, given the usual lack of information on the complex conformational features determined by the nature of the carrier and the mode of ligation. Using the Herpes simplex virus glycoprotein D-1 epitope (Leu9-Lys-Nle-Ala- Asp-Pro-Asn-Arg-Phe-Arg-Gly-Lys-Asp-Leu22) as a model, we have performed a detailed conformational analysis on the free epitope peptide in solution and on three constructs in which the epitope was conjugated to sequential oligopeptide carriers {Ac-[Lys-Aib-Gly]4-OH (SOC 4)} (through either a thioether or an amide bond; Ac: acetyl) and polytuftsin oligomers {H-[Thr-Lys-Pro-Lys-Gly]4-NH2 (T20)}, (through a thioether bond). The analysis of the epitope conformation in the parent protein, in carrier-conjugated and free form, suggests that the β-turn structure of the -Asp13-Pro-Asn-Arg16- segment is highly conserved and independent of the epitope form. However, small conformational variations were observed at the C-terminal part of the epitope, depending on the nature of the carrier.

Original languageEnglish (US)
Pages (from-to)383-399
Number of pages17
JournalBiopolymers - Peptide Science Section
Volume84
Issue number4
DOIs
StatePublished - Jul 7 2006

Keywords

  • Carrier-conjugated epitopes
  • Conformation of conjugated epitope peptides
  • Glycoprotein D-1 epitope
  • Sequential oligopeptide carriers
  • Synthetic carriers
  • Tetratuftsin carrier

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Biomaterials
  • Organic Chemistry

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