Gauche⁺ side-chain orientation as a key factor in the search for an immunogenic peptide mixture leading to a complete fully protective vaccine

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• 作者：Adriana Bermú ; dez^a ; ^c ; Dayana Calderon^a ; Armando Moreno-Vranich^a ; Hannia Almonacid^a ; Manuel A. Patarroyo^a ; ^c ; André ; s Poloche^a ; Manuel E. Patarroyo^a ; ^b ; ^{mepatarr@gmail.com" class="auth_mail}
• 关键词：pMHC ; peptide&ndash ; major histocompability class ; TCR ; T-cell receptor ; cHABP ; conserved high activity binding peptide ; mHABP ; modified high activity binding peptide ; FPIPS ; full protection-inducing protein structure ; VHLLAI ; very high long-lasting antibody-inducing ; HIPI ; highly immunogenic protection-inducing
• 刊名：Vaccine
• 出版年：11 April, 2014
• 年：2014
• 卷：32
• 期：18
• 页码：2117-2126
• 全文大小：3557 K

文摘

Topological and stereo-electron characteristics are essential in major histocompability class II-peptide-T-cell receptor (MHC-p-TCR) complex formation for inducing an appropriate immune response. Modified high activity binding peptides (mHABPs) were synthesised for complete full protection antimalarial vaccine development producing a large panel of individually fully protection-inducing protein structures (FPIPS) and very high long-lasting antibody-inducing (VHLLAI) mHABPs. Most of those which did not interfere, compete, inhibit or suppress their individual VHLLAI or FPIPS activity contained or displayed a polyproline II-like (PPII_L) structure when mixed. Here we show that amino acid side-chains located in peptide binding region (PBR) positions p3 and p7 displayed specific electron charges and side-chain m>gauchem>^m>+m> orientation for interacting with the TCR. Based on the above, and previously described physicochemical principles, non-interfering, long-lasting, full protection-inducing, multi-epitope, multistage, minimal subunit-based chemically synthesised mHABP mixtures can be designed for developing vaccines against diseases scourging humankind, malaria being one of them.