Synthesis of a multivalent, multiepitope vaccine construct.
A major challenge to contemporary peptide chemistry is to reproduce highly complex active sites or complexes of native proteins. In addition to the need for the combination of different peptide fragments, true protein mimics designed for therapeutic use frequently require the incorporation of multiple copies of given active domains in a biologically relevant spatial arrangement. Perhaps the best examples for this line of drug design are subunit vaccine candidates against extracellular domains of ion-channel proteins. One of our earlier constructs containing four copies of the ectodomain of the M2 protein of influenza virus together with two independent T-helper cell epitopes induced protective antibody production in mice. Here I describe an improved synthesis of the M2-based multiepitope and multivalent peptide construct. In general, the synthetic strategy outlined here can serve as a model for the orthogonal N-terminal and side-chain-protecting scheme during the preparation of large, complex peptides or small, engineered proteins.
Otvos
Laszlo
L
Sbarro Institute for Cancer Research and Molecular Medicine, Temple University, Philadelphia, PA, USA.
D000595:Amino Acid Sequence; D000818:Animals; D015195:Drug Design; D000939:Epitopes / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D051379:Mice; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D022223:Vaccines, Subunit / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology; D014763:Viral Matrix Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D000086082:Viroporin Proteins
D000939:Epitopes; D010446:Peptide Fragments; D022223:Vaccines, Subunit; D014763:Viral Matrix Proteins; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins