1. Convergent synthetic methodology for the construction of self-adjuvanting lipopeptide vaccines using a novel carbohydrate scaffold
- Author
-
Istvan Toth, Pavla Simerska, and Vincent Fagan
- Subjects
Scaffold ,Organic Chemistry ,Lipopeptide ,cycloadditon reaction ,Carbohydrate ,Combinatorial chemistry ,Full Research Paper ,Cycloaddition ,Epitope ,3. Good health ,lcsh:QD241-441 ,Chemistry ,chemistry.chemical_compound ,multivalent glycosystems ,chemistry ,lcsh:Organic chemistry ,amino acid lipidation ,Peptide vaccine ,peptide vaccine ,Moiety ,lcsh:Q ,lcsh:Science ,tetrapropargyl glucopyranose - 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.
- Published
- 2014