title: Investigation toward multi-epitope vaccine candidates using native chemical ligation.
abstract: We applied native chemical ligation (NCL) method to the synthesis of highly pure lipid-core peptide (LCP) vaccines to attach various peptide epitopes. In the case of the synthesis of LCP vaccine with two different peptide epitopes, LCP moieties having two free Cys and two protected Cys derivatives (S-acetamidemethyl-Cys, (Cys(Acm)), N-methylsulfonylethyloxycarbonyl-Cys (Msc-Cys), or 1,3-thiazolidine-4-carboxylic acid (Thz)) on oligolysine branches were prepared in order to couple two different epitopes by stepwise NCL. It was found that the difficulty in NCL of first two peptide antigen was associated with the steric hindrance. Using Thz instead of Cys(Acm) and Msc-Cys was important to reduce the steric hindrance and improve NCL yield.
authors.affiliation: School of Molecular and Microbial Sciences (SMMS), The University of Queensland, Brisbane QLD 4072, Australia. y.fujita@uq.edu.au
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Fujita
authors.forename: Peter M
authors.initials: PM
authors.lastname: Moyle
authors.forename: Suzanne
authors.initials: S
authors.lastname: Hieu
authors.forename: Pavla
authors.initials: P
authors.lastname: Simerska
authors.forename: Istvan
authors.initials: I
authors.lastname: Toth
mesh_terms: D000577:Amides / Q000737:chemistry; D003545:Cysteine / Q000737:chemistry; D018985:Epitopes, B-Lymphocyte / Q000737:chemistry / Q000276:immunology*; D055666:Lipopeptides / Q000138:chemical synthesis; D022541:Streptococcal Vaccines / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology; D014612:Vaccines / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology*; D022223:Vaccines, Subunit / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology
chemical_list: D000577:Amides; D018985:Epitopes, B-Lymphocyte; D055666:Lipopeptides; D022541:Streptococcal Vaccines; D014612:Vaccines; D022223:Vaccines, Subunit; D003545:Cysteine