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Biological Chemistry

Ligating Peptides Through Lysine

Lysine modified to contain a thiol group can be used instead of cysteine to perform native chemical ligation en route to synthesizing peptides

by Jyllian N. Kemsley
September 21, 2009 | APPEARED IN VOLUME 87, ISSUE 38

A lysine modified to contain a thiol group can be used instead of cysteine to perform native chemical ligation, a common technique for synthesizing peptides, reports a research group led by Xue-Wei Liu and Chuan-Fa Liu of Nanyang Technological University, in Singapore (J. Am. Chem. Soc., DOI: 10.1021/ja905491p). The method allows for installation of lysines bearing posttranslational modifications or biophysical tags in proteins. The Singapore scientists used aspartic acid as a starting point to synthesize a lysine derivative with a thiol group at the γ-carbon of the side chain—the thiol group mediates reactions at the α- and ε-amino groups on the amino acid. The researchers next attached the modified lysine as the N-terminal amino acid residue of a synthetic peptide, and then ligated that peptide to a second synthetic peptide through the lysine α-amino group. Finally, they modified the lysine by attaching either ubiquitin or biotin to the side chain through the ε-amino group and removed the thiol (shown above). The approach should significantly expand the usefulness of native chemical ligation for synthesizing complex protein molecules, the researchers say.



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