Synthesis and construction of a novel multiple peptide conjugate system: strategy for a subunit vaccine design

作者: Robert A. Boykins , Manju Joshi , Chaing Syin , Subhash Dhawan , Hira Nakhasi

DOI: 10.1016/S0196-9781(99)00172-2

关键词: Peptide sequenceConjugateCombinatorial chemistryGel electrophoresisPeptideCysteineAmino acidChemistryMolecular massPeptide synthesisBiochemistryPhysiologyEndocrinologyCellular and Molecular Neuroscience

摘要: We describe the design and synthesis of a novel well characterized multi-peptide conjugate (MPC) system containing antigens from human malaria parasite Tat protein HIV type-1 (HIV-1-Tat). Construction MPC utilizes Fmoc solid-phase peptide coupled with solution chemistry. In first phase, core template that serves as primary anchor for attachment multiple is synthesized. Serine(trityl) lysine branches epsilon groups blocked during chain assembly are incorporated forming tetrameric core. Cysteine whose side thiol to couple haloacetyl or S-protected peptides added complete template. Modification coupling solvent, addition key amino acid derivatives (N-[1-hydroxy-4-methoxybenzyl]) in sequence allows base on molecular mass greater than 7500 kDa. Base then reacted high performance liquid chromatography purified generate conjugates masses 10 13 constructs thus formed further by matrix assisted laser desorption-time flight spectroscopy (MALDI-MS), analysis, size exclusion chromatography, SDS-polyacrylamide gel electrophoresis (PAGE). To our knowledge, this report describing chemically defined potential development synthetic subunit vaccines.

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