Selection of Natural Peptide Ligands for Copper-Catalyzed Azide–Alkyne Cycloaddition Catalysis
| Autor: | Lindsay Dahora, Kelly Gamble, M. G. Finn, Allison G. Aioub |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
Azides
Stereochemistry Biomedical Engineering Pharmaceutical Science Alkyne Bioengineering Ligands 010402 general chemistry 01 natural sciences Catalysis chemistry.chemical_compound Solid-Phase Synthesis Techniques Pharmacology chemistry.chemical_classification Cycloaddition Reaction 010405 organic chemistry Ligand Organic Chemistry Substrate (chemistry) Combinatorial chemistry Cycloaddition 0104 chemical sciences Organic reaction chemistry Alkynes Azide Peptides Copper Biotechnology |
| Zdroj: | Bioconjugate Chemistry. 28:1693-1701 |
| ISSN: | 1520-4812 1043-1802 |
| DOI: | 10.1021/acs.bioconjchem.7b00161 |
| Popis: | The copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction is a powerful tool for making connections in both organic reactions and biological systems. However, the use of this ligation process in living cells is limited by the toxicity associated with unbound copper ions. As an initial attempt to create peptide-based accelerating ligands capable of cellular expression, we performed synthesis and selection for such species on solid-phase synthesis beads bearing both candidate ligand and alkyne substrate. A simple histidine-containing motif (HXXH) was identified, and found after solution-phase optimization to produce single-turnover systems showing moderate rate acceleration over the ligand-free reaction. CuAAC reaction rates and yields for different alkynes were found to respond to the peptide ligands, demonstrating a substrate scope beyond what was used for the selection steps, but also illustrating the potential difficulty in evolving a general CuAAC catalyst. |
| Databáze: | OpenAIRE |
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