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

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 (Leu(9)-Lys-Nle-Ala-Asp-Pro-Asn-Arg-Phe-Arg-Gly-Lys-Asp-Leu(22)) 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)-NH(2) (T20)}, (through a thioether bond). The analysis of the epitope conformation in the parent protein, in carrier-conjugated and free form, suggests that the beta-turn structure of the -Asp(13)-Pro-Asn-Arg(16)- 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.

Peptide vaccine candidates against classical swine fever virus: T cell and neutralizing antibody responses of dendrimers displaying E2 and NS2–3 epitopes

“…Multimerization has long been recognized as an effective strategy for enhancing the response of peptides in immunization experiments1–3. Among the different approaches such as simple polymerization4, or conjugation to sequential oligopeptide carriers2, 5, or display on lysine scaffolds6, 7, incorporation into dendrimeric systems such as the MAP platforms pioneered by Tam1, 8, 9 has proven particularly successful for immunological and microbiological applications9–12.…”

Design, structural, and immuno‐analytical properties of antigenic bioconjugates comprising a β‐amyloid‐plaque specific epitope

“…It was also determined that in the case of OT20-conjugate the C-terminus attachment site of the epitope was more flexible than in the case of SOC conjugate. 19 In the present study, the influence of carriers on the antibody recognition of a much shorter epitope, Ab(4-10), was investigated by preparation of OT20, MAP, and SOC conjugates. The key feature of these oligopeptide carriers is the amplification of the epitope peptide in a well-defined manner, all conjugates containing four copies of the Ab(4-10) epitope attached to the carrier either through the N-or C-terminus.…”

Effect of Conjugation with Polypeptide Carrier on the Enzymatic Degradation of Herpes Simplex Virus Glycoprotein D Derived Epitope Peptide

“…Another epitope of gD-1 has been identified by monoclonal antibodies and located in the 268-287 region (19,20). It was shown that the minimal epitope of this region in the HSV gD-1 was the important in the immunological recognition, as has been proven in the case of another sequence of the same protein (22).…”