Chemobacterial Synthesis of a Sialyl-Tn Cyclopeptide Vaccine Candidate. Article - Septembre 2017

Emeline Richard, Carlo Pifferi, Michele Fiore, Eric Samain, Sébastien Fort, Olivier Renaudet, Bernard Priem, Audrey Le Gouellec

Emeline Richard, Carlo Pifferi, Michele Fiore, Eric Samain, Sébastien Fort, Olivier Renaudet, Bernard Priem, Audrey Le Gouellec, « Chemobacterial Synthesis of a Sialyl-Tn Cyclopeptide Vaccine Candidate.  », ChemBioChem, septembre 2017, pp. 1730-1734. ISSN 1439-4227

Abstract

A conjugatable form of the tumour-associated carbohydrate antigen sialyl-Tn (Neu5Ac-α-2,6-GalNAc) was efficiently produced in Escherichia coli. Metabolically engineered E. coli strains overexpressing the 6-sialyltransferase gene of Photobacterium sp. and CMP-Neu5Ac synthetase genes of Neisseria meningitidis were cultivated at high density in the presence of GalNAc-α-propargyl as the exogenous acceptor. The target disaccharides, which were produced on the scale of several hundreds of milligrams, were then conjugated by using copper(I)-catalysed azide-alkyne cycloaddition click chemistry to a fully synthetic and immunogenic scaffold with the aim to create a candidate anticancer vaccine. Four sialyl-Tn epitopes were introduced on the upper face of an azido-functionalised multivalent cyclopeptide scaffold, the lower face of which was previously modified by an immunogenic polypeptide, PADRE. The ability of the resulting glycoconjugate to interact with oncofoetal sialyl-Tn monoclonal antibodies was confirmed in ELISA assays.

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