Synthesis of Peptides and Proteins without Cysteine Residues by Native Chemical Ligation Combined with Desulfurization
| Autor: | Philip E. Dawson, Liang Z. Yan |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Barnase
Alanine chemistry.chemical_classification biology Chemistry Aminobutyrates Proteins General Chemistry Thioester Native chemical ligation Biochemistry Catalysis Amino acid Residue (chemistry) Ribonucleases Colloid and Surface Chemistry Bacterial Proteins Bacteriocins Methods biology.protein Cysteine Chemical ligation Peptides |
| Zdroj: | Journal of the American Chemical Society. 123:526-533 |
| ISSN: | 1520-5126 0002-7863 |
| DOI: | 10.1021/ja003265m |
| Popis: | The highly chemoselective reaction between unprotected peptides bearing an N-terminal Cys residue and a C-terminal thioester enables the total and semi-synthesis of complex polypeptides. Here we extend the utility of this native chemical ligation approach to non-cysteine containing peptides. Since alanine is a common amino acid in proteins, ligation at this residue would be of great utility. To achieve this goal, a specific alanine residue in the parent protein is replaced with cysteine to facilitate synthesis by native chemical ligation. Following ligation, selective desulfurization of the resulting unprotected polypeptide product with H(2)/metal reagents converts the cysteine residue to alanine. This approach, which provides a general method to prepare alanyl proteins from their cysteinyl forms, can be used to chemically synthesize a variety of polypeptides, as demonstrated by the total chemical syntheses of the cyclic antibiotic microcin J25, the 56-amino acid streptococcal protein G B1 domain, and a variant of the 110-amino acid ribonuclease, barnase. |
| Databáze: | OpenAIRE |
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