Butelase-Mediated Macrocyclization ofd -Amino-Acid-Containing Peptides
| Autor: | Giang K. T. Nguyen, Xinya Hemu, James P. Tam, Jun-Ping Quek |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
chemistry.chemical_classification Staphylococcus aureus DNA ligase Macrocyclic Compounds Stereochemistry Peptide Microbial Sensitivity Tests General Medicine General Chemistry 010402 general chemistry 01 natural sciences Catalysis Chemical space Anti-Bacterial Agents 0104 chemical sciences 03 medical and health sciences Residue (chemistry) 030104 developmental biology Enzyme chemistry Escherichia coli D-amino acid Amino Acids Peptides |
| Zdroj: | Angewandte Chemie International Edition. 55:12802-12806 |
| ISSN: | 1433-7851 |
| DOI: | 10.1002/anie.201607188 |
| Popis: | Macrocyclic compounds have received increasing attention in recent years. With their large surface area, they hold promise for inhibiting protein-protein interactions, a chemical space that was thought to be undruggable. Although many chemical methods have been developed for peptide macrocyclization, enzymatic methods have emerged as a promising new economical approach. Thus far, most enzymes have been shown to act on l-peptides; their ability to cyclize d-amino-acid-containing peptides has rarely been documented. Herein we show that macrocycles consisting of d-amino acids, except for the Asn residue at the ligating site, were efficiently synthesized by butelase 1, an Asn/Asp-specific ligase. Furthermore, by using a peptide-library approach, we show that butelase 1 tolerates most of the d-amino acid residues at the P1'' and P2'' positions. |
| Databáze: | OpenAIRE |
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