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A New Circular Helicoid-Type Sequential Oligopeptide carrier for Assembling Multiple Antigenic Peptides

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Self-Assembling Peptide Systems in Biology, Medicine and Engineering

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Abstract

A novel class of oligopeptide carriers termed Sequential Oligopeptide Carriers (SOCs) is presented. SOCs are formed either by the Lys-Aib-Gly or the Aib-Lys-Aib-Gly sequential motif. By varying the number of the repeating units, carriers of the general formula either SOCn-I, (Lys-Aib-Gly)n, or SOCn-II, (Aib-Lys- Aib-Gly)n, where n=2–7, are prepared. The carriers adopt a predetermined secondary structure of 3 10-helix, which is given by the presence of Aib, an unnatural amino acid with a known propensity to induce ordered helicoid backbone. This helicoidal structure contributes to the reduction of steric hindrance and conformational restrictions of the carrier, and thus allows antigenic peptides to retain their original structure as confirmed by 1HNMR and molecular modeling studies. Four antigenic sequences were selected to assess the utility of SOCs-conjugates, either as antigens in solid-phase immunoassays, or as immunogens in eliciting specific anti-peptide antibodies and producing an immune spreading:

  1. (i)

    the [Ala76] decapeptide derivative of the main immunogenic region (MIR, Trp67-Asn-Pro-Ala-Asp-Tyr-Gly-Gly-Lys76) of the Torpedo nicotinic acetylcholine receptor (AChR),

  2. (ii)

    the gp63-SRYD octapeptide fragment (Ile250-Ala-Ser-Arg-Tyr-Asp-Gln-Leu257) of the gp63, the major surface glycoprotein of Leishmania,

  3. (iii)

    the B-cell epitopes of the La/SSB antigen, TLHKAFKGSIFVVFDSIESA (145–164) ANNGNLQLRNKEVTWEVLEG (289–308), VTWEVLEGEVEKEALKKI (301–318) and GSGKGKVQFQGKKTKF (349–364), major targets of anti-La/SSB antibodies in primary Sjögren’s syndrome (pSS) and systemic lupus erythematosus (SLE), and

  4. (iv)

    the PPGMRPP heptapeptide, found in several copies in the Sm and U1RNP antigens, main targets of anti-Sm/U1 RNP antibodies in SLE. The spatial arrangement and the regular secondary structure of the multiepitopic SOCs-conjugates result in such an orientation and accessibility of the antigens that favour their recognition by antibodies in immunoassays and by the cells of the immune process.

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Authors and Affiliations

  1. Department of Chemisty, University of Ioannina, P.O.BOX 1186, 54110, Ioannina, Greece

    Marta Sakarellos-Daitsiotis, Vassilios Tsikaris & Constantinos Sakarellos

Authors
  1. Marta Sakarellos-Daitsiotis
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  2. Vassilios Tsikaris
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  3. Constantinos Sakarellos
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© 2002 Kluwer Academic Publishers

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Sakarellos-Daitsiotis, M., Tsikaris, V., Sakarellos, C. (2002). A New Circular Helicoid-Type Sequential Oligopeptide carrier for Assembling Multiple Antigenic Peptides. In: Self-Assembling Peptide Systems in Biology, Medicine and Engineering. Springer, Dordrecht. https://doi.org/10.1007/0-306-46890-5_19

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  • DOI: https://doi.org/10.1007/0-306-46890-5_19

  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-0-7923-7090-1

  • Online ISBN: 978-0-306-46890-2

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