Synthesis of relaxin‐2 and insulin‐like peptide 5 enabled by novel tethering and traceless chemical excision
| Autor: | Vasily M. Gelfanov, John P. Mayer, Xu Yang, Fa Liu, Richard D. DiMarchi, Binbin Kou, Alexander N. Zaykov, Kishore Thalluri |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Proteolysis Lysine Molecular Conformation Peptide Cleavage (embryo) 01 natural sciences Biochemistry 03 medical and health sciences Structural Biology Drug Discovery medicine Humans Insulin Molecular Biology Pharmacology chemistry.chemical_classification medicine.diagnostic_test 010405 organic chemistry Chemistry Relaxin Organic Chemistry Proteins Biological activity General Medicine Combinatorial chemistry 0104 chemical sciences 030104 developmental biology Enzyme Covalent bond Molecular Medicine Relaxin/insulin-like family peptide receptor 2 |
| Zdroj: | Journal of Peptide Science. 23:455-465 |
| ISSN: | 1099-1387 1075-2617 |
| DOI: | 10.1002/psc.3010 |
| Popis: | This report presents an entirely chemical, general strategy for the synthesis of relaxin-2 and insulin-like peptide 5. Historically, these two peptides have represented two of the more synthetically challenging members of the insulin superfamily. The key synthetic steps involve two sequential oxime ligations to covalently link the individual A-chain and B-chain, followed by disulfide bond formation under aqueous, redox conditions. This is followed by two chemical reactions that employ diketopiperazine cyclization-mediated cleavage and ester hydrolysis to liberate the connecting peptide and the heterodimeric product. This approach avoids the conventional iodine-mediated disulfide bond formation and enzyme-assisted proteolysis to generate biologically active two-chain peptides. This novel synthetic strategy is ideally suited for peptides such as relaxin and insulin-like peptide 5 as they possess methionine and tryptophan that are labile under strong oxidative conditions. Additionally, these peptides possess multiple arginine and lysine residues that preclude the use of trypsin-like enzymes to obtain biologically active hormones. This synthetic methodology is conceivably applicable to other two-chain peptides that contain multiple disulfide bonds. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text