TY - JOUR
T1 - Influence of sequential oligopeptide carriers on the bioactive structure of conjugated epitopes
T2 - 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
AU - Krikorian, Dimitrios
AU - Stavrakoudis, Athanassios
AU - Biris, Nikolaos
AU - Sakarellos, Constantinos
AU - Andreu, David
AU - De Oliveira, Eliandre
AU - Mezö, Gábor
AU - Majer, Zsuzsa
AU - Hudecz, Ferenc
AU - Welling-Wester, Sytske
AU - Cung, Manh Thong
AU - Tsikaris, Vassilios
PY - 2006
Y1 - 2006
N2 - 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.
AB - 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.
KW - Carrier-conjugated epitopes
KW - Conformation of conjugated epitope peptides
KW - Glycoprotein D-1 epitope
KW - Sequential oligopeptide carriers
KW - Synthetic carriers
KW - Tetratuftsin carrier
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U2 - 10.1002/bip.20486
DO - 10.1002/bip.20486
M3 - Article
C2 - 16493659
AN - SCOPUS:33745524890
SN - 0006-3525
VL - 84
SP - 383
EP - 399
JO - Biopolymers - Peptide Science Section
JF - Biopolymers - Peptide Science Section
IS - 4
ER -