Synthesis of N-terminally linked protein dimers and trimers by a combined native chemical ligation-CuAAC click chemistry strategy.
A novel method for the synthesis of N-terminally linked protein multimers is reported. Azide and alkyne thioesters were synthesized for the N-terminal modification of expressed proteins using native chemical ligation (NCL). Proteins modified by these moieties can be joined together to form homodimers and homotrimers via Cu(I)-catalyzed azide-alkyne [3 + 2] cycloaddition (CuAAC) click chemistry. The orthogonal nature of this reaction allows the production of protein heteromultimers, and this is demonstrated by synthesis of a protein heterodimer.
Xiao
Junpeng
J
Interdisciplinary Biochemistry Graduate Program and Department of Chemistry, Indiana University, Bloomington, Indiana 47405, USA.
Tolbert
Thomas J
TJ
D000480:Alkynes / Q000737:chemistry; D001386:Azides / Q000737:chemistry; D003500:Cyclization; D010446:Peptide Fragments / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D055503:Protein Multimerization; D011506:Proteins / Q000737:chemistry*
D000480:Alkynes; D001386:Azides; D010446:Peptide Fragments; D011108:Polymers; D011506:Proteins