title: Convergent synthetic methodology for the construction of self-adjuvanting lipopeptide vaccines using a novel carbohydrate scaffold.
abstract: A novel convergent synthetic strategy for the construction of multicomponent self-adjuvanting lipopeptide vaccines was developed. A tetraalkyne-functionalized glucose derivative and lipidated Fmoc-lysine were prepared by novel efficient and convenient syntheses. The carbohydrate building block was coupled to the self-adjuvanting lipidic moiety (three lipidated Fmoc-lysines) on solid support. Four copies of a group A streptococcal B cell epitope (J8) were then conjugated to the glyco-lipopeptide using a copper-catalyzed cycloaddition reaction. The approach was elaborated by the preparation of a second vaccine candidate which incorporated an additional promiscuous T-helper epitope.
authors.affiliation: The University of Queensland, School of Chemistry and Molecular Biosciences, Cooper Road, St. Lucia QLD 4072, Australia.
authors.forename: Vincent
authors.initials: V
authors.lastname: Fagan
authors.affiliation: The University of Queensland, School of Chemistry and Molecular Biosciences, Cooper Road, St. Lucia QLD 4072, Australia ; The University of Queensland, School of Pharmacy, Pharmacy Australia Centre of Excellence, Cornwall Street, Woolloongabba, QLD 4072, Australia.
authors.forename: Istvan
authors.initials: I
authors.lastname: Toth
authors.affiliation: The University of Queensland, School of Chemistry and Molecular Biosciences, Cooper Road, St. Lucia QLD 4072, Australia.
authors.forename: Pavla
authors.initials: P
authors.lastname: Simerska
keywords: amino acid lipidation; cycloadditon reaction; multivalent glycosystems; peptide vaccine; tetrapropargyl glucopyranose