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Chemobacterial Synthesis of a Sialyl‐Tn Cyclopeptide Vaccine Candidate
Authors:Dr. Emeline Richard  Dr. Carlo Pifferi  Dr. Michele Fiore  Dr. Eric Samain  Dr. Audrey Le Gouëllec  Dr. Sébastien Fort  Prof. Olivier Renaudet  Dr. Bernard Priem
Affiliation:1. Université Grenoble Alpes and CNRS, CERMAV, Grenoble, France;2. Université Grenoble Alpes and CNRS, DCM, Grenoble, France;3. Laboratoire TIMC-IMAG CNRS UMR 5525, Faculté de Médecine, Grenoble, France
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.
Keywords:antigens  chemobacterial synthesis  peptides  sialyl–  Tn  vaccine conjugates
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