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        Modeling and Virtual Screening of Antisense Peptides Targeting the Divergent Region of Tumor-Associated MT1-MMP Protein

        Bowen Tan,Yijie Zhou,Zhilei Song,Yinxuan Peng,Fang Wu,Yue Kang,Xiaomin Liu,Li Zeng,Tingting Huang,Zongying Liu,Lili Xiong,Zhiyun Guo,Jian Cui,Canquan Mao 대한화학회 2015 Bulletin of the Korean Chemical Society Vol.36 No.9

        Membrane type-1 matrix metalloproteinase (MT1-MMP; 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 MT1-MMP- or MMP-based 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 MT1-MMP. The modeling of the three-dimensional structure of mature MT1-MMP and the finding of MT1-MMP targeted peptides by virtual screening are highly desired. In this study, the three-dimensional structure of mature MT1-MMP 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 MT1-MMP, which was found by multiple alignment of the whole MMP family. The antisense peptide library was virtually screened against the constructed three-dimensional model of MT1-MMP. The top 20 novel peptides were further studied, which were found well docked with MT1-MMP at the region of DEGTEEET, again confirming their specific binding to MT1-MMP. Preliminary study of one of the top-ranked peptide SFLLSPFV showed that it could inhibit the viabilities of MG63 and MDA-MB-231 tumor cells. We thus not only successfully modeled the three-dimensional structure of mature MT1-MMP but also provided a new way for the finding of peptide candidates targeting MT1-MMP based on antisense peptide library.

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        Antifungal mechanisms of ε-poly-L-Lysine with different molecular weights on Saccharomyces cerevisiae

        Ying Hou,Fengping Wang,Zhilei Tan,Jiandong Cui,Shiru Jia 한국화학공학회 2020 Korean Journal of Chemical Engineering Vol.37 No.3

        ε-Poly-L-lysine (ε-PL) is a natural antimicrobial cationic peptide. Antimicrobial activity of ε-PL is closely related to its molecular weight (Mw). However, the antimicrobial mechanisms of ε-PL with different Mws are still vague. In this study, Saccharomyces cerevisiae was used as the model system to analyze the mechanism from these three aspects: cell wall, cell membrane, and metabolism. The results showed that high-Mw ε-PL (1-3 kDa and >3 kDa) and commercial ε-PL product caused cell wall lesions, and significantly improved cell membrane permeability compared to low-Mw ε-PL (<1 kDa), resulting in leaking of the protoplasm through the pores and cell death. Furthermore, metabolomics analysis showed that high-Mw ε-PL (1-3 kDa and >3 kDa) and product displayed higher inhibition effect on the glycolysis pathway and tricarboxylic cycle than that of low-Mw ε-PL (<1 kDa).

      • KCI등재

        Characterization of Bacteriostatic Sausage Casing: A Composite of Bacterial Cellulose Embedded with ε-Polylysine

        Huixia Zhu,Shiru Jia,Hongjiang Yang,Weihua Tang,Zhilei Tan,Yuanyuan Jia 한국식품과학회 2010 Food Science and Biotechnology Vol.19 No.6

        The feasibility of a novel bacteriostatic sausage casing made of bacterial cellulose (BC) embedded with ε-polylysine (ε-PL) was evaluated. The ε-PL/BC composite was prepared by immersing BC tubes in ε-PL solution and its characteristics were analyzed with Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD),and atomic force microscopy (AFM) techniques, respectively. The results suggested that ε-PL molecules were incorporated into the cellulose fiber networks and the ε-PL/BC composite might have a novel unique structure. No significant loss of antimicrobial activity was observed even after autoclaving at 121℃ for 30 min and the oxygen permeability was far below than that of polyethylene (PE) and polyvinyl alcohol (PVA) membrane. Its tensile strength was 51.8 MPa. The ε-PL/BC composite exhibits bacteriostatic and/or bacteriocidal activities against a broad spectrum of Gram-positive and Gram-negative bacteria; as a result, an extended shelf life than controls was observed for sausage packaged with the ε-PL/BC composite.

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