检索结果-南通市图书馆

Cobalamin-dependent radical S-adenosyl-L-methionine protein functions with a partner to successively methylate tricyclic indole alkaloid for chuangxinmycin maturation and derivatization

引用

Science China Chemistry 2025年第1期 308-316页

作者： Sili Wang Jiancheng Huang Yanan Du Wei Huang Yufeng Xue Xiaokun Xu Guannan Zhong Yuanyuan Shi Bin Hong Xiaoying Bian Wen Liu state key laboratory of Chemical Biology Shanghai Institute of Organic Chemistry University of Chinese Academy of SciencesChinese Academy of Sciences state key laboratory of Microbial Technology Shandong University National Health Commission (NHC) key laboratory of Biotechnology for Microbial drugs Institute of Medicinal BiotechnologyChinese Academy of Medical Science & Peking Union Medical College

Cobalamin(Cbl)-dependent radical S-adenosyl-L-methionine(SAM) proteins constitute the largest collection of the radical SAM superfamily that has hundreds of thousands of individual members. Many of these proteins are involved in the biosynthesis of pharmaceutically important natural products to catalyze chemically demanding reactions. In the biosynthetic pathway of chuangxinmycin(CXM), a unique indole alkaloid antibiotic with potent anti-infective activity, functionalization of the characteristic thiopyrano[4,3,2-cd]indole scaffold by regio-and stereoselective C3-methylation is believed to rely on a Cbl-dependent radical process, which, however, remained to be reconstituted biochemically. We here report the dissection of this enzymatic process, which requires the incorporation of Cxm8, a Cbl-dependent radical SAM protein, with Cxm9, a DUF5825family protein that shares no homology to any proteins of known functions. Cxm8 and Cxm9 function together by forming an unexpected heterodimeric complex that selectively catalyzes C3-methylation of the tricyclic indole-S-hetero ring system in a successive manner, achieving CXM and a recently identified, C3-dimethylated congener. Detailed biochemical characterization,isotope labeling, structural simulation and bioinformatics analysis rationalized the catalysis of the Cxm8/Cxm9 complex and particularly the necessity of the DUF5825 protein for C3-methylase activity. This is the first example that a Cbl-dependent protein acts with a partner to exhibit radical SAM activity.

关键词：

来源：

同方期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Modifying metabolic and immune hallmarks of cancer by a copper complex

引用

Science China Chemistry 2025年

作者： Chengyan Chu Yunhua Zhang Chengyuan Qian Xiuzhi Yang Yicun Shang Zijian Guo Xiaoyong Wang state key laboratory of Pharmaceutical Biotechnology School of Life Sciences Nanjing University state key laboratory of Coordination Chemistry School of Chemistry and Chemical Engineering Nanjing University

Metabolic adaptation of cancer cells is a key tactic for maintaining their tumorigenicity and viability in the tumor immune microenvironment （TIME）.Concurrent modulation on the metabolic pathway and immune system could change the living condition of cancer cells and potentiate the efficacy of anticancer drugs.A copper complex （DDCu） was designed to influence the energy metabolism of cancer cells and reshape the *** restrained the production and transportation of lactate by inhibiting the expression of lactate dehydrogenase and monocarboxylate transporter 4,thereby altering the metabolic pathway of cancer cells and improving the acidic tumor ***,DDCu was reduced to Cu+by cellular glutathione to react with lipoylated proteins of the tricarboxylic acid cycle and destabilize the Fe–S cluster proteins,leading to the aggregation of dihydrolipoamide S-acetyltransferase and cuproptosis in cancer ***,DDCu promoted the polarization of macrophages from the M2 to M1 phenotype,activated CD4+and CD8+T cells,and reversed the *** a result,DDCu inhibited the tumor growth through a synergy between metabolic regulation and immunomodulation.

关键词：

来源：

同方期刊数据库评论

在线全文

同方期刊数据库

学校读者我要写书评

暂无评论

Dissecting the cell microenvironment of ovarian endometrioma through single-cell RNA sequencing

引用

Science China Life Sciences 2025年第1期 116-129页

作者： Jiangpeng Wu Siyu Xia Wenting Ye Yan Sun Jing Cai Fubing Yu Haiping Wen Xiuwei Yi Taikang Li Mingwei Chen Jiayun Chen Ge Song Chuanbin Yang Yali Song Jigang Wang Department of Reproductive Medicine Dongguan Maternal and Child Health Care Hospital Department of Urology and Shenzhen Clinical Research Centre for GeriatricsShenzhen People's HospitalSouthern University of Science and Technology state key laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs Artemisinin Research Centerand Institute of Chinese Materia MedicaChina Academy of Chinese Medical Sciences Reproductive Medicine Center Foshan Women and Children Hospital state key laboratory of Antiviral drugs School of PharmacyHenan University

Ovarian endometrioma（OE）, also known as “chocolate cysts,” is a cystic mass that develops in the ovaries due to endometriosis and is a common gynecological condition characterized by the growth of endometrial tissue outside the uterus, leading to symptoms such as dysmenorrhea, pelvic pain, and infertility. However, the precise molecular and cellular mechanisms driving this pathophysiology remain largely unknown, posing challenges for diagnosis and treatment. Here, we employed integrated single-cell transcriptomic profiling of over 52,000 individual cells from endometrial tissues of OE patients and healthy donors and identified twelve major cell populations. We identified notable alterations in cell type-specific proportions and molecular signatures associated with OE. Notably, the activation of IGFBP5+macrophages with pro-inflammatory properties, NK cell exhaustion, and aberrant proliferation of IQCG+and KLF2+epithelium are key features and may be the potential mechanisms underlying the pathogenesis of OE. Collectively, our data contribute to a better understanding of OE at the single cell level and may pave the way for the development of novel therapeutic strategies.

关键词： ovary high-throughput sequencing transcriptomics gene expression analysis ligand-receptor analysis

来源：

同方期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Transient chemical-mediated epigenetic modulation confers unrestricted lineage potential on human primed pluripotent stem cells

引用

Science China Life Sciences 2025年

作者： Shi Chen Yuanyuan He Lejun Lv Bei Liu Cheng Li Hongkui Deng Jun Xu Department of Cell Biology School of Basic Medical Sciences Peking University Stem Cell Research Center Peking University Health Science Center Peking University Academy of Advanced Interdisciplinary Studies Peking University BeiCell Therapeutics School of Life Sciences Center for Bioinformatics Center for Statistical Science Peking University MOE Engineering Research Center of Regenerative Medicine School of Basic Medical Sciences State Key Laboratory of Natural and Biomimetic Drugs Peking University Health Science Center and the MOE Key Laboratory of Cell Proliferation and Differentiation College of Life Sciences Peking-Tsinghua Center for Life Sciences Peking University

Human primed pluripotent stem cells are capable of generating all the embryonic ***,their extraembryonic trophectoderm potentials are *** remains unclear how to expand their developmental potential to trophectoderm *** we show that transient treatment with a cocktail of small molecule epigenetic modulators imparts trophectoderm lineage potentials to human primed pluripotent stem cells while preserving their embryonic *** chemically treated cells can generate trophectoderm-like cells and downstream trophoblast stem cells,diverging into syncytiotrophoblast and extravillous trophoblast *** and CUT&Tag analyses reveal that these induced cells share transcriptional profiles with in vivo trophectoderm and cytotrophoblast,and exhibit reduced H3K27me3 modification at gene loci specific to trophoblast lineages compared with primed pluripotent *** exploration highlighted the critical roles of epigenetic modulators HDAC2,EZH1/2,and KDM5s in the activation of trophoblast lineage *** findings demonstrate that transient epigenetic resetting activates unrestricted lineage potential in human primed pluripotent stem cells,and offer new mechanistic insights into human trophoblast lineage specification and in vitro models for studying placental development and related disorders.

关键词：

来源：

同方期刊数据库评论

在线全文

同方期刊数据库

学校读者我要写书评

暂无评论

C–H bond activation in the total syntheses of natural products

引用

Science China Chemistry 2016年第9期59卷 1109-1125页

作者： Pengyu Tao Yanxing Jia state key laboratory of natural and Biomimetic drugs School of Pharmaceutical Sciences Peking University

The transition metal-mediated C–H bond activation has emerged as a powerful and ideal method for the total syntheses of natural products and pharmaceuticals, and has had a significant impact on synthetic planning and strategy in complex natural *** this review, we describe selected recent examples of the transition metal-mediated C–H bond activation strategies for the rapid syntheses of natural products.

关键词： C-H activation transition metal natural product total synthesis

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Protosappanin A exerts anti-neuroinflammatory effect by inhibiting JAK2-STAT3 pathway in lipopolysaccharide-induced BV2 microglia

引用

Chinese Journal of natural Medicines 2017年第9期15卷 674-679页

作者： WANG Li-Chao LIAO Li-Xi ZHAO Ming-Bo DONG Xin ZENG Ke-Wu TU Peng-Fei state key laboratory of natural and Biomimetic drugs School of Pharmaceutical Sciences Peking University state key laboratory of natural Medicines China Pharmaceutical University

Microglial activation and resultant neuroinflammatory response are implicated in various brain diseases including Alzheimer's disease and Parkinson's disease. Treatment with anti-neuroinflammatory agents could provide therapeutic benefits for such disorders. Protosappanin A(PTA) is a major bioactive ingredient isolated from Caesalpinia sappan L.. In this work, the anti-neuroinflammatory effects of PTA on LPS-stimulated BV2 cells were investigated and the underlying mechanisms were explored. Results showed that PTA significantly inhibited the production of TNF-α and IL-1β in LPS-activated BV2 microglia. Moreover, the mR NA expressions of IL-6, IL-1β, and MCP-1 were reduced by PTA in a dose-dependent manner. Furthermore, PTA suppressed JAK2/STAT3-dependent inflammation pathway through down-regulating the phosphorylation of JAK2 and STAT3, as well as STAT3 nuclear translocation against LPS treatment. These observations suggested a novel role for PTA in regulating LPS-induced neuroinflammatory injuries.

关键词： Neuroinflammation BV2 microglia Lipopolysaccharide Protosappanin A JAK2-STAT3

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

An efficient ionic liquid supported divergent assembly of 3,6-branched glucosamine-containing pentasaccharide

引用

Chinese Chemical Letters 2014年第12期25卷 1525-1530页

作者： Ze-Shen Gao Sheng Sun Wei Li Qing Ma Qing Li Zhong-Jun Li The state key laboratory of natural and Biomimetic drugs School of Pharmaceutical SciencesPeking University

We utilized the glycosyl acceptor tagging method with ionic liquid support for synthesis of the core segment of Clostridium botulinum C2 toxin ligand through a divergent synthetic strategy without chromatographic *** total yield was 57.1% and the reaction was completed in 10 *** efficient ionic liquid supported glycosylation and purification procedure was applied for the synthesis of branched glucosamine-containing oligosaccharides for the first time,which expanded the scope of ionic liquid supported synthesis of biologically important oligosaccharides.

关键词： Ionic liquid Oligosaccharide Rapid assembling

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Loss of silencing activity caused by 5′-terminal modification with D-/L-isonucleotide(isoNA) or locked nucleic acid(LNA) could not be restored by 5′-terminal phosphorylation

引用

Science China Chemistry 2014年第2期57卷 329-334页

作者： HUANG Ye CHEN Zhuo WANG Zhuo LI YaTing CHEN Yue YANG ZhenJun ZHANG LiHe The state key laboratory of natural and Biomimetic drugs School of Pharmaceutical Sciences Peking University

In this study,a series of 5′-phosphorylated siRNAs with D-/L-isonucleotide(isoNA)or locked nucleic acid(LNA)incorporated at the 5′-terminus were *** was found that after incorporating either isoNA or LNA at the 5′-terminus of the antisense strand or sense strand,the silencing activity of modified strands has been inhibited,which cannot be recovered by phosphorylation at the 5′-terminus;however,the silencing activity of unmodified strand to its own target was *** work indicates that the isoNA and LNA modification at 5′-terminus can interfere with the strand selection during the RISC assembling process,and the disturbance of the 5′-phosporylation should not be the only viable mechanism.

关键词： isonucleotide locked nucleic acid (LNA) 5'-terminal phosphorylation

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Recent advances in the preparation of Fmoc-SPPS-based peptide thioester and its surrogates for NCL-type reactions

引用

Science China Chemistry 2017年第2期60卷 201-213页

作者： Hongxing Li Suwei Dong state key laboratory of natural and Biomimetic drugs School of Pharmaceutical Sciences Peking University Beijing 100191 China

Solid phase peptide synthesis(SPPS)based on Fmoc chemistry has become a commonly used technique in peptide chemistry,as it can be easily conducted using automated machine,and not requiring highly toxic HF in comparison to *** the fast development in the emerging field of protein chemical synthesis,many efforts have been endeavored aiming to find more efficient methods for preparing peptide fragments required in ligation *** review briefly summarizes recent advances in the engineering and modification of Fmoc-SPPS-derived peptides,which can be used as the N-terminal fragments in a native chemical ligation(NCL)or NCL-type ligation reactions.

关键词： native chemical ligation Fmoc-SPPS peptide thioester protein chemical synthesis

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

A novel method for the synthesis of sulfur substituted-cyclopyrophosphate of cADPR analogs

引用

Chinese Chemical Letters 2014年第12期25卷 1583-1585页

作者： Ren-Min Wu Na Qi Yu-Wen Jia Zhu Guan Liang-Ren Zhang Li-He Zhang Zhen-Jun Yang state key laboratory of natural and Biomimetic drugs School of Pharmaceutical SciencesPeking University

A facile and efficient protocol for the synthesis of sulfur substituted-cyclopyrophosphate of cIDPRE（P_S^1-cIDPRE） was *** key step was the cyclization process which was completed by the sulfur substituted cyclizati... 详细信息

关键词： cADPR cIDPRE Phosphoramidite strategy Cyclopyrophosphate

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

欢迎您,

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

请选择保存的检索档案：

请选择收藏分类：

通借通还

欢迎您,

建议与咨询 留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

请选择保存的检索档案： 新增检索档案 确定 取消

请选择收藏分类： 新增自定义分类 确定 取消

通借通还

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

请选择保存的检索档案：

请选择收藏分类：