| Title | Constructing Cyclic Peptides Using an On-Tether Sulfonium Center |
| Authors | Song, Chunli Hou, Zhanfeng Jiao, Zijun Liu, Zhaodi Lian, Chenshan Zhang, Min Liang, Wei Yin, Feng Li, Zigang |
| Affiliation | Shenzhen Bay Lab, Pingshan Translat Med Ctr, Shenzhen, Peoples R China Peking Univ, Shenzhen Grad Sch, Sch Chem Biol & Biotechnol, Key Lab Chem Genom, Shenzhen, Peoples R China Anhui Med Univ, Affiliated Hosp 1, Dept Radiat Oncol, Hefei, Peoples R China |
| Keywords | METHIONINE CYSTEINE HELIX |
| Issue Date | Sep-2022 |
| Publisher | JOVE-JOURNAL OF VISUALIZED EXPERIMENTS |
| Abstract | In recent years, cyclic peptides have attracted increasing attention in the field of drug discovery due to their excellent biological activities, and, as a consequence, they are now used clinically. It is, therefore, critical to seek effective strategies for synthesizing cyclic peptides to promote their application in the field of drug discovery. This paper reports a detailed protocol for the efficient synthesis of cyclic peptides using on-resin or intramolecular (intermolecular) bisalkylation. Using this protocol, linear peptides were synthesized by taking advantage of solid-phase peptide synthesis with cysteine (Cys) and methionine (Met) coupled simultaneously on the resin. Further, cyclic peptides were synthesized via bisalkylation between Met and Cys using a tunable tether and an on-tether sulfonium center. The whole synthetic route can be divided into three major processes: the deprotection of Cys on the resin, the coupling of the linker, and the cyclization between Cys and Met in a trifluoroacetic acid (TFA) cleavage solution. Furthermore, inspired by the reactivity of the sulfonium center, a propargyl group was attached to the Met to trigger thiol-yne addition and form a cyclic peptide. After that, the crude peptides were dried and dissolved in acetonitrile, separated, and then purified by high-performance liquid chromatography (HPLC). The molecular weight of the cyclic peptide was confirmed by liquid chromatography-mass spectrometry (LC-MS), and the stability of the cyclic peptide combination with the reductant was further confirmed using HPLC. In addition, the chemical shift in the cyclic peptide was analyzed by H-1 nuclear magnetic resonance (H-1 NMR) spectra. Overall, this protocol aimed to establish an effective strategy for synthesizing cyclic peptides. |
| URI | http://hdl.handle.net/20.500.11897/668228 |
| ISSN | 1940-087X |
| DOI | 10.3791/64289 |
| Indexed | SCI(E) |
| Appears in Collections: | 深圳研究生院待认领 |
