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Target binding and residence:a new determinant of DNA double-strand break repair pathway choice in CRISPR/Cas9 genome editing 被引量:2
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作者 Yili FENG Sicheng LIU +1 位作者 Ruodan CHEN Anyong XIE 《Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)》 SCIE CAS CSCD 2021年第1期73-86,共14页
The clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated protein 9(Cas9)is widely used for targeted genomic and epigenomic modifications and imaging in cells and organisms,and holds trem... The clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated protein 9(Cas9)is widely used for targeted genomic and epigenomic modifications and imaging in cells and organisms,and holds tremendous promise in clinical applications.The efficiency and accuracy of the technology are partly determined by the target binding affinity and residence time of Cas9-single-guide RNA(sgRNA)at a given site.However,little attention has been paid to the effect of target binding affinity and residence duration on the repair of Cas9-induced DNA double-strand breaks(DSBs).We propose that the choice of DSB repair pathway may be altered by variation in the binding affinity and residence duration of Cas9-sgRNA at the cleaved target,contributing to significantly heterogeneous mutations in CRISPR/Cas9 genome editing.Here,we discuss the effect of Cas9-sgRNA target binding and residence on the choice of DSB repair pathway in CRISPR/Cas9 genome editing,and the opportunity this presents to optimize Cas9-based technology. 展开更多
关键词 CRISPR/Cas9 genome editing Double-strand break(DSB)repair pathway choice target binding affinity target residence
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Potential application of proteolysis targeting chimera(PROTAC)modification technology in natural products for their targeted protein degradation
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作者 Guliang Yang Haiyan Zhong +3 位作者 Xinxin Xia Zhiwen Qi Chengzhang Wang Shiming Li 《Food Science and Human Wellness》 SCIE 2022年第2期199-207,共9页
There are numerous evaluations of natural products,of which majority are food bioactives,performed up to date for their various health beneficial activities via targeting specific proteins.However,the direct identific... There are numerous evaluations of natural products,of which majority are food bioactives,performed up to date for their various health beneficial activities via targeting specific proteins.However,the direct identification of a targeted protein remains unexplored for natural occurring compounds.Proteolysis targeting chimera(PROTAC)is a type of bifunctional chimeric molecules that can directly degrade the binding proteins targeted by bioactive molecules in an ubiquitin-proteasome pathway.As the agents in protein degradation dependent on ubiquitin ligase,the bifunctional molecule connects the target protein ligand and E3 ligase ligand together via an appropriate linker.It is highly selective and efficient to induce the ubiquitin-mediated degradation of targeted binding proteins.Therefore,it has been demonstrated that the PROTAC technology has broad application in the modulation of the target protein level.In this review,we outlined the advances in PROTAC combined molecule compounds,summarized its quantitative structure-activity relationship,and finally reviewed the methods applied in identifying the target proteins of natural products.We hope it will provide an insightful application of PROTAC techniques in the target protein identification of natural products including food bioactive molecules. 展开更多
关键词 PROTAC LIGAND Natural products target binding
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Natural Products and Derivatives Targeting at Cancer Energy Metabolism:A Potential Treatment Strategy 被引量:2
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作者 Qi-qi WANGI Ming-xue LI +4 位作者 Chen LI Xiao-xia GU Meng-zhu ZHENG Li-xia CHEN Hua LI 《Current Medical Science》 SCIE CAS 2020年第2期205-217,共13页
In the 1920s,Dr Otto Warburg first suggested the significant difference in energy metabolism between malignant cancer cells and adjacent normal cells.Tumor cells mainly adopt the glycolysis as energy source to maintai... In the 1920s,Dr Otto Warburg first suggested the significant difference in energy metabolism between malignant cancer cells and adjacent normal cells.Tumor cells mainly adopt the glycolysis as energy source to maintain tumor cell growth and biosynthesis under aerobic conditions.Investigation on energy metabolism pathway in cancer cells has aroused the interest of cancer researchers all around the world.In recent years,plentiful studics suggest that targeting the peculiar cancer energy metabolic pathways,including glycolysis,mitochondrial respiration,amino acid metabolism,and fatty acid oxidation may be an effective strategy to starve cancer cells by blocking essential nutrients.Natural products (NPs)are considered as the “treasure trove of small molecules drugs” and have played an extremely remarkable role in the discovery and development of anticancer drugs.And numerous NPs have been reported to act on cancer energy metabolism targets.Herein,a comprehensive overview about cancer energy metabolism targets and their natural-occurring inhibitors is prepared. 展开更多
关键词 cancer energy metabolism cancer therapy natural products binding targets inhibitors
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The Observation of FSH’s Cellular Internalization
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作者 Jizhong Han Jianwen Hu +3 位作者 Lanlan Liu Fei Chen Xian Zhang Bin Zeng 《Journal of Biosciences and Medicines》 2016年第12期37-41,共6页
Follicle stimulating hormone (FSH) is a kind of glycoprotein gonadotropin, and plays an important role in the diagnosis and treatment of infertility. Follicle stimulating hormone receptor (FSHR) is a kind of G protein... Follicle stimulating hormone (FSH) is a kind of glycoprotein gonadotropin, and plays an important role in the diagnosis and treatment of infertility. Follicle stimulating hormone receptor (FSHR) is a kind of G protein coupled receptor (GPCR), found in the ovary and testes, and its activation is required for the hormonal operation during the breeding period. In this study, an experimental model of FSHR mediated FSH into cell membrane, which exhibited a phenomenon of fluorescent localized on cell surfaces internalized into cell interior, was established to verify biological activity of FSH. 展开更多
关键词 FSH Receptor target binding Celluar Internalization
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Targeted peptide-Au cluster binds to epidermal growth factor receptor (EGFR) in both active and inactive states: a clue for cancer inhibition through dual pathways 被引量:4
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作者 Peng Zhang Jiao Zhai +3 位作者 Xueyun Gao Hongkang Zhao Wenyong Su Lina Zhao 《Science Bulletin》 SCIE EI CSCD 2018年第6期349-355,共7页
The epidermal growth factor receptor (EGFR) has become an important target protein in anticancer drug development. Meanwhile, peptide-Au cluster has been proposed as potential targeted nano-drug assembled by targeti... The epidermal growth factor receptor (EGFR) has become an important target protein in anticancer drug development. Meanwhile, peptide-Au cluster has been proposed as potential targeted nano-drug assembled by targeting peptide. Here, we designed and synthesized a novel peptide-Au cluster as AuloPeptides to target to EGFR. We found AumPeptides could target to the natural binding sites of all EGFRs at mem- brane in both active and inactive states by molecular simulations. Its targeted ability was further verified by the co-localization and blocking experiments. We also study the configuration modifications of both active and inactive EGFRs after binding by AumPeptides. For active EGFR, the absorbed AuloPeptide5 might replace the natural ligand in EGFR endocytosis process. Then, the peptide-Au cluster in endochylema could inhibit the cancer relating enzyme activity including thioredoxin reductasel (TrxR1) and induce the oxidative stress mediated apoptosis in tumor cells. For inactive EGFR, it was retained in inactive state by Au10 Peptides binding to inhibit dimerization of EGFR for anticancer. Both pathways might be applied in anticancer drug development based on the theoretical and experimental study here. 展开更多
关键词 peptide-Au cluster EGFR targeted binding Anticancer
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