Synthesis of N-terminally linked protein and peptide dimers by native chemical ligation.
Dimerization can be utilized to double the molecular weight of proteins and peptides and potentially increase their avidity of binding to target receptors. These dimerization effects may be utilized to increase in vivo half-lives in a manner similar to PEGylation and may also improve biological activity. In this paper, we report a new strategy for the synthesis of N-terminally linked protein and peptide homodimers utilizing native chemical ligation to conjugate a short dithioester linker to the N-terminal cysteines of protein and peptide monomers to form dimers in a single step. This strategy is general and has been applied to the production of dimers from three recombinantly expressed polypeptides, the IgG binding domain Protein G, an HIV entry inhibitor peptide C37H6, and human interleukin-1 receptor antagonist (IL-1ra). The biological activities of the C37H6 and IL-1ra dimers produced by these methods were retained or even slightly increased when compared to their corresponding monomers.
Department of Chemistry, Indiana University, Bloomington, 47405, United States.
Junpeng
J
Xiao
Brian S
BS
Hamilton
Thomas J
TJ
Tolbert
D019281:Dimerization; D004952:Esters / Q000138:chemical synthesis / Q000737:chemistry*; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry; D015394:Molecular Structure; D008970:Molecular Weight; D009419:Nerve Tissue Proteins / Q000138:chemical synthesis* / Q000737:chemistry; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry
D004952:Esters; C029152:G-substrate; D007074:Immunoglobulin G; D009419:Nerve Tissue Proteins; D010455:Peptides