Design and synthesis of plant cyclopeptide Astin C analogues and investigation of their immunosuppressive activity |
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| Authors: | Fei Li Xi-Xi Guo Guang-Zhi Zeng Wei-Wei Qin Bo Zhang Ning-Hua Tan |
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| Affiliation: | 1. State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, People’s Republic of China;2. State Key Laboratory of Natural Medicines, Department of TCMs Pharmaceuticals, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, People’s Republic of China;3. University of Chinese Academy of Sciences, Beijing 10049, People’s Republic of China |
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| Abstract: | To further investigate on the structure-activity relationships of immunosuppressive Astin C, seventeen analogues 1–17 were designed and synthetized via amino acid substitution strategy by the solid-phase peptide synthesis method for the first time. In comparison with Astin C (IC50?=?12.6?±?3.3?μM), only compounds 2 (IC50?=?38.4?±?16.2?μM), 4 (IC50?=?51.8?±?12.7?μM), 5 (IC50?=?65.2?±?15.6?μM), and 8 (IC50?=?61.8?±?12.4?μM) exhibited immunosuppressive activity in the Lymph node cells of mice. These results showed that the Astin C analogues containing D-amino acid residues, hydrophobic long-chain alkyl substituents, and aryl substituents performed better than those carrying hydrophilic amino acid residues and short-chain alkyl substituents. Moreover compounds 15, 16, and 17 had no immunosuppressive activity, which suggested that cis-3,4-dichlorinated proline played an important role in the immunosuppressive activity of Astin C. |
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| Keywords: | Astin C analogues Solid-phase peptide synthesis Immunosuppressive activity |
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