Investigation toward multi-epitope vaccine candidates using native chemical ligation.
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.
Fujita
Yoshio
Y
School of Molecular and Microbial Sciences (SMMS), The University of Queensland, Brisbane QLD 4072, Australia. y.fujita@uq.edu.au
Moyle
Peter M
PM
Hieu
Suzanne
S
Simerska
Pavla
P
Toth
Istvan
I
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
D000577:Amides; D018985:Epitopes, B-Lymphocyte; D055666:Lipopeptides; D022541:Streptococcal Vaccines; D014612:Vaccines; D022223:Vaccines, Subunit; D003545:Cysteine