An Oxazetidine Amino Acid for Chemical Protein Synthesis by Rapid, Serine-Forming Ligations

作者：Pusterla Ivano^*; Bode Jeffrey W

来源：Synthesis (Germany), 2016, 48(3): A29-A31.

DOI：10.1038/nchem.2282

Amide-forming ligation reactions allow the chemical synthesis of proteins by the union of unprotected peptide segments, and enable the preparation of protein derivatives not accessible by expression or bioengineering approaches. The native chemical ligation (NCL) of thioesters and N-terminal cysteines is unquestionably the most successful approach, but is not ideal for all synthetic targets. Here we describe the synthesis of an Fmoc-protected oxazetidine amino acid for use in the alpha-ketoacid-hydroxylamine (KAHA) amide ligation. When incorporated at the N-terminus of a peptide segment, this fourmembered cyclic hydroxylamine can be used for rapid serine-forming ligations with peptide alpha-ketoacids. This ligation operates at low concentration (100 mu M-5 mM) and mild temperatures (20-25 degrees C). The utility of the reaction was demonstrated by the synthesis of S100A4, a 12 kDa calcium-binding protein not easily accessible by NCL or other amideforming reactions due to its primary sequence and properties.

• 出版日期2016-2