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

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.

Rheology of peptide‐ and protein‐based physical hydrogels: Are everyday measurements just scratching the surface?

“…Physically crosslinked, solid injectable hydrogels can be developed from peptides, proteins, or polymers. With rapid advances in peptide, protein, polymer, and protein–polymer conjugate synthesis and materials development, rheological characterization has become an increasingly important tool to obtain more information about the viscoelastic and flow properties of hydrogels based on peptides, proteins, and polymers. Common rheological studies conducted on hydrogel materials include measurement of shear storage modulus (G′) (qualitatively the material stiffness), loss modulus (G″) (qualitatively the material liquid‐like flow properties), and loss factor tan ( δ ) (the ratio of liquid‐like behavior to solid‐like behavior), measured as functions of time, oscillatory frequency, and oscillatory strain.…”

Influenza virus H5N1 hemagglutinin (HA) T‐cell epitope conjugates: design, synthesis and immunogenicity

“…Oxidation of the 2‐amino‐alcohol group of serine (coupled to the C ‐terminus Lys‐N ε H 2 group) by NaIO 4 resulted in the formation of an aldehyde group: Aqueous solution of the epitope (10 m M ) was diluted with imidazole buffer (50 m M , pH 7 and chloride counter‐ion) and NaIO 4 (12 m M ) was added in the mixture. After 4 min, the oxidation was quenched by adding ethyleneglycol solution (100 m M )16–18. The epitopes were isolated by semipreparative RP‐HPLC and characterized by analytical RP‐HPLC and ESI‐MS (Tables 1 and 3).…”

“…The aldehyde‐epitope was present in a 1.5‐fold molar excess over each reactive group on the carrier. Reaction progress was followed by ESI‐MS and the product was purified by semipreparative HPLC and characterized by analytical HPLC and ESI‐MS16–18 (Tables 2 and 4), (Figure 3).…”

MAP dendrimer elicits antibodies for detecting rat and mouse GH‐binding proteins

“…New presentation strategies for the immunogen include oligomerization, dextran bead coupling, and T-helper epitope conjugation [22] as well as construction of lipo-MAPs entrapped in liposomes [23]. Progress in the synthesis of MAPs with branched architectures [24] and in chemoselective peptide ligation [25,26] has also been made.…”