Peptide Ligasos—-Tools for Peptide Synthesis

摘要

Following the first chemical fonnation of a peptide bond by Theodor Curtius in 1881 in the laboratory of Hermann Kolbe in Leipzig, chemical pepiidc synthesis developed over the next ninety years culminating in the first total synthesis of an enzvine.Ribonuclease A (RNaseA). composed of 124 amino acid residues was constructed by condensation of fragments in solution as well as in solid-phase synthesis. Roughly ten years later Yajima and fujii synthesized RNase A accoiding to an improved conventionalsynthetie strategy and obtained the first crystalline synthetie enzyme having full enzymalic activity. But an ideal, universally applicable method lor chemical formation of the peptide bond has still not been found. Since chemosyn-thetic reactions are typically conducted with residues haying chirai centers, racemization is a constant concern. Even stepwise chain extension using urethane proiecting groups, which are supposed to prevent racemization, may be affected: chemical linkage of peptide fragmentsis yet more unreliable.