6533b7d5fe1ef96bd1263dc6
RESEARCH PRODUCT
Towards a fully synthetic MUC1-based anticancer vaccine: efficient conjugation of glycopeptides with mono-, di-, and tetravalent lipopeptides using click chemistry.
Yufen ZhaoLei ShiZhi-hua HuangYan-mei LiHorst KunzHui Caisubject
Synthetic vaccineMagnetic Resonance SpectroscopyCarbohydrate chemistryMolecular Sequence DataAntineoplastic AgentsCancer VaccinesCatalysisEpitopeCell Linechemistry.chemical_compoundLipopeptidesMiceSolid-phase synthesisAnimalsHumansAntigens Tumor-Associated CarbohydrateVaccines SyntheticMembrane GlycoproteinsMolecular StructureOrganic ChemistryMucin-1GlycopeptidesLipopeptideGeneral ChemistryCombinatorial chemistryGlycopeptidechemistryClick chemistryClick ChemistryConjugateProtein Bindingdescription
Abstract The membrane-bound tumor-associated glycoprotein MUC1 is aberrantly glycosylated in cancer cells compared with normal cells, and is therefore considered an attractive target for cancer immunotherapy. However, tumor-associated glycopeptides from MUC1 do not elicit a sufficiently robust immune response. Therefore, antitumor vaccines were developed, which consist of MUC1 glycopeptides as the B epitopes and immune-stimulating toll-like receptor 2 (TLR 2) lipopeptide ligands. These fully synthetic vaccine candidates were prepared by solid-phase synthesis of the MUC1 glycopeptides. The Pam(3) Cys lipopeptide, also synthesized on solid-phase, was C-terminally coupled to oligovalent lysine cores, which N-terminally incorporate O-propargyl oligoethylene glycol acyl side chains. The MUC1 glycopeptides and lipopeptide lysine constructs were then conjugated by click chemistry to give oligovalent synthetic vaccines. Oligovalent glycopeptide-lipopeptide conjugates are considered more immunogenic than their monovalent analogues.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2011-04-27 | Chemistry (Weinheim an der Bergstrasse, Germany) |