Use of model peptide reactions for the characterization of kinetically controlled ligation
| Autor: | Duhee Bang, Yoonjin Kwon, Joongoo Lee, Brad L. Pentelute |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Biomedical Engineering
Pharmaceutical Science Bioengineering Peptide Large target Chemical synthesis chemistry.chemical_compound HIV Protease Methods Organic chemistry Combinatorial Chemistry Techniques Reactivity (chemistry) Pharmacology chemistry.chemical_classification Esterification Aryl Organic Chemistry Proteins Combinatorial chemistry Kinetics chemistry Muramidase Lysozyme Ligation Peptides Biotechnology |
| Zdroj: | Bioconjugate chemistry. 22(8) |
| ISSN: | 1520-4812 |
| Popis: | Since the introduction of kinetically controlled ligation (KCL), a chemoselective reaction between a peptide-(α)thioarylester and a Cys-peptide-(α)thioalkylester, KCL has been utilized for the total chemical synthesis of large proteins (i.e., lysozyme and HIV-protease) by providing fully convergent synthetic routes. Although KCL has the potential to become an important chemistry for protein synthesis, the principle of KCL is not fully characterized. In particular, prior work on KCL has focused on the reactivity difference of the two different -(α)thioester forms-alkyl vs aryl. Another equally important feature of KCL, Xaa-Cys ligation sites, has not been investigated. The work reported here describes combinatorial KCL reactions using model peptides to dissect the interplay of the Xaa(1), Xaa(2), -(α)thioarylester, and -(α)thioalkylester. Results from these studies provide fundamental insights into the KCL reaction, and will lead to the optimal synthetic route for the routine chemical synthesis of large target protein molecules. |
| Databáze: | OpenAIRE |
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