Chemical Synthesis of Monomeric, Dimeric and Tetrameric Forms of the Ectodomain of Influenza Matrix 2 Protein

Abstract

The highly conserved ectodomain of M2 protein (M2e) of influenza virus A is one of the most studied vaccine targets for induction of cross-strain protection. It has been reported that the native form of M2 is a homo-tetramer linked by disulfide bonds and that antibodies reactive to this form correlate with M2-mediated protection. Although vaccine constructs mimicking the quaternary structure of M2 have been described, the chemical syntheses of disulfide-linked dimeric and tetrameric forms of M2e have not yet been reported. By exploiting orthogonal chemistry during the syntheses, we successfully assembled dimeric and tetrameric forms of M2e but found that the antibodies that they elicited had..