Synthetic Approaches for Total Chemical Synthesis of Proteins and Protein-Like Macromolecules of Branched Architecture

Serafim      Papas; Constantinos      Strongylis; Vassilios      Tsikaris

Abstract

The progress achieved both in the solid and liquid phase of the synthetic methodologies for peptides, permitted the application of various chemistries for preparing totally synthetic proteins and protein-like macromolecules of branched architecture. Polypeptides with molecular masses in the 10-25 kDa range have been successfully prepared using either the step by step and fragment condensation or the chemoselective ligation methods. Amide, thioether, disulfide, thioester, hydrazone, oxime and thiazolidine linkages have been employed in such syntheses. Fully active proteins or macromolecules mimicking particular protein properties especially in immunology have been synthesized in high purity and large quantities. The branched constructs have found numerous applications in immunology due to their contribution in overcoming the very low ability of short linear peptides to react specifically with antibodies or to induce an immune response. The advantages over almost all the other methods of using synthetic carriers for developing potent antigens and immunogens have placed this approach at the center of extensive research activities. This review focuses on the concept and synthetic strategies suitable for assembling proteins or protein-like macromolecules of branched architecture with application in protein function studies and immunology.

Keywords: electrospray mass spectrometry, template-assembled synthetic proteins, trifluoroacetic acid, calcium-binding protein, thioether ligation