Bulletin of the Korean Chemical Society | |
Modeling and Virtual Screening of Antisense Peptides Targeting the Divergent Region of Tumor‐Associated MT1‐MMP Protein | |
Lili Xiong1  Canquan Mao1  Yue Kang1  Tingting Huang1  Zhiyun Guo1  Jian Cui1  Zongying Liu1  Bowen Tan1  Yinxuan Peng1  Xiaomin Liu1  Li Zeng1  Yijie Zhou1  Zhilei Song1  Fang Wu1  | |
[1] Laboratory of Molecular Evolution and Applied Biology School of Life Science and Engineering, Southwest Jiaotong University Chengdu 610031 China | |
关键词: ; MT1‐; MMP ; Antisense peptide; Virtual screening; Docking; Modeling; | |
DOI : 10.1002/bkcs.10421 | |
学科分类:化学(综合) | |
来源: Korean Chemical Society | |
【 摘 要 】
Membrane typeâ1 matrix metalloproteinase (MT1âMMP; also known as MMP14) is a key enzyme involved in tumor invasion and metastasis, and is a potential target for drug discovery for cancer therapy. However, till now there is no MT1âMMPâ or MMPâbased anticancer drugs in the market mainly because of the high conservation of the MMP family and also because there is no elucidated crystal structure for the mature MT1âMMP. The modeling of the threeâdimensional structure of mature MT1âMMP and the finding of MT1âMMP targeted peptides by virtual screening are highly desired. In this study, the threeâdimensional structure of mature MT1âMMP is constructed by homology and de novo modeling and later rationalized and optimized by molecular dynamics simulations. An antisense peptide library was constructed against the divergent sense peptide DEGTEEET in the specific region of MT1âMMP, which was found by multiple alignment of the whole MMP family. The antisense peptide library was virtually screened against the constructed threeâdimensional model of MT1âMMP. The top 20 novel peptides were further studied, which were found well docked with MT1âMMP at the region of DEGTEEET, again confirming their specific binding to MT1âMMP. Preliminary study of one of the topâranked peptide SFLLSPFV showed that it could inhibit the viabilities of MG63 and MDAâMBâ231 tumor cells. We thus not only successfully modeled the threeâdimensional structure of mature MT1âMMP but also provided a new way for the finding of peptide candidates targeting MT1âMMP based on antisense peptide library.
【 授权许可】
Unknown
【 预 览 】
Files | Size | Format | View |
---|---|---|---|
RO201901236933993ZK.pdf | 85KB | download |