Macrocyclization and labeling of helix-loop-helix peptide with intramolecular bis-thioether linkage
| Autor: | Ikuo Fujii, Daisuke Fujiwara, Hidekazu Kitada, Toshio Nishihara |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
chemistry.chemical_classification
010405 organic chemistry Organic Chemistry Biophysics Alkyne Peptide General Medicine 010402 general chemistry 01 natural sciences Biochemistry Combinatorial chemistry Cycloaddition 0104 chemical sciences Amino acid Biomaterials chemistry.chemical_compound chemistry Thioether Intramolecular force Click chemistry Azide |
| Zdroj: | Biopolymers. 106:415-421 |
| ISSN: | 0006-3525 |
| DOI: | 10.1002/bip.22826 |
| Popis: | Conformationally constrained peptides have been developed as an inhibitor for protein-protein interactions (PPIs), and we have de novo designed cyclized helix-loop-helix (cHLH) peptide with a disulfide bond consisting of 40 amino acids to generate molecular-targeting peptides. However, synthesis of long peptides has sometimes resulted in low yield according to the respective amino acid sequences. Here we developed a method for efficient synthesis and labeling for cHLH peptides. First, we synthesized two peptide fragments and connected them by the copper-mediated alkyne and azide cycloaddition (CuAAC) reaction. Cyclization was performed by bis-thioether linkage using 1,3-dibromomethyl-5-propargyloxybenzene, and subsequently, the cHLH peptide was labeled with an azide-labeled probe. Finally, we designed and synthesized a peptide inhibitor for the p53-HDM2 interaction using a structure-guided design and successfully labeled it with a fluorescent probe or a functional peptide, respectively, by click chemistry. This macrocyclization and labeling method for cHLH peptide would facilitate the discovery of de novo bioactive ligands and therapeutic leads. © 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 415-421, 2016. |
| Databáze: | OpenAIRE |
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