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Rational Optimizations of the Marine-Derived Peptide Sungsanpin as Novel Inhibitors of Cell Invasion |
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| Authors: | Anpeng Li Jihua Zou Xiaobin Zhuo Shuai Chen Xiaoyun Chai Conghao Gai Xiang Li Qingjie Zhao Yan Zou |
| Institution: | 1. School of Pharmacy, Naval Medical University, Shanghai, 200433 China
These authors contributed equally to this work.;2. Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian Province 350122 China These authors contributed equally to this work.;3. School of Pharmacy, Naval Medical University, Shanghai, 200433 China |
| Abstract: | Cancer metastasis, including cell invasion, is a major cause of poor clinical outcomes and death in numerous cancer patients. In recent years, many efforts have been made to develop potent therapeutic molecules from naturally derived peptides. Sungsanpin is a naturally derived lasso peptide that inhibits A549 cell invasion. We aimed to evaluate the potential of sungsanpin derivatives as candidates for anti-invasion drugs. We synthesized an analog of sungsanpin (Sun A) using a solid-phase peptide synthesis strategy (SPPS) and further modified its structure to improve its anti-invasion activity. All peptides were tested for their proliferative inhibition and anti-invasion activities in the A549 cell lines. Octapeptide S3 and cyclooctapeptide S4 upregulated the expression of TIMP-1 and TIMP-2 mRNA effectively and thus improved the inhibitory effect on the invasion of A549 cells. The two peptides can inhibit the invasion of A549 cells by up to 60 %, suggesting that they have potential as lead molecules for the development of peptide inhibitors. |
| Keywords: | lasso peptide Sungsanpin peptide drug design cancer invasion TIMP-1/TIMP-2 |