Synthesis of proteins by native chemical ligation.
A simple technique has been devised that allows the direct synthesis of native backbone proteins of moderate size. Chemoselective reaction of two unprotected peptide segments gives an initial thioester-linked species. Spontaneous rearrangement of this transient intermediate yields a full-length product with a native peptide bond at the ligation site. The utility of native chemical ligation was demonstrated by the one-step preparation of a cytokine containing multiple disulfides. The polypeptide ligation product was folded and oxidized to form the native disulfide-containing protein molecule. Native chemical ligation is an important step toward the general application of chemistry to proteins.
Scripps Research Institute, La Jolla, CA 92037.
P E
PE
Dawson
T W
TW
Muir
I
I
Clark-Lewis
S B
SB
Kent
D000595:Amino Acid Sequence; D006801:Humans; D016209:Interleukin-8 / Q000138:chemical synthesis* / Q000737:chemistry; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D011487:Protein Conformation; D017510:Protein Folding; D011506:Proteins / Q000138:chemical synthesis* / Q000737:chemistry
D016209:Interleukin-8; D011506:Proteins