Protein assembly by orthogonal chemical ligation methods.
Chemical synthesis harbors the potential to provide ready access to natural proteins as well as to create nonnatural ones. The Staudinger ligation of a peptide containing a C-terminal phosphinothioester with a peptide containing an N-terminal azide gives an amide with no residual atoms. This method for amide bond formation is orthogonal and complementary to other ligation methods. Herein, we describe the first use of the Staudinger ligation to couple peptides on a solid support. The fragment thus produced is used to assemble functional ribonuclease A via native chemical ligation. The synthesis of a protein by this route expands the versatility of chemical approaches to protein production.
Department of Chemistry, University of Wisconsin, Madison, Wisconsin 53706, USA.
Bradley L
BL
Nilsson
Robert J
RJ
Hondal
Matthew B
MB
Soellner
Ronald T
RT
Raines
D000596:Amino Acids / Q000737:chemistry; D007700:Kinetics; D019906:Nuclear Magnetic Resonance, Biomolecular; D010446:Peptide Fragments / Q000138:chemical synthesis*; D011487:Protein Conformation; D012259:Ribonuclease, Pancreatic / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism
D000596:Amino Acids; D010446:Peptide Fragments; D012259:Ribonuclease, Pancreatic