检索结果-南通市图书馆

Disulfide bridge-targeted metabolome mining unravels an antiparkinsonian peptide

Acta Pharmaceutica Sinica B 2024年第2期14卷 881-892页

作者： Zhiwu Tong Xiahong Xie Huiming Ge Ruihua Jiao Tingting Wang Xincun Wang Wenying Zhuang Gang Hu renxiang tan State Key Laboratory of Pharmaceutical Biotechnology Institute of Functional BiomoleculesSchool of Life SciencesNanjing UniversityNanjing 210023China State Key Laboratory Cultivation Base for TCM Quality and Efficacy Nanjing University of Chinese MedicineNanjing 210023China Institute of Microbiology Chinese Academy of SciencesBeijing 100101China

Peptides are a particular molecule class with inherent attributes of some small-molecule drugs and macromolecular biologics,thereby inspiring continuous searches for peptides with therapeutic and/or agrochemical potentials.However,the success rate is decreasing,presumably because many interesting but less-abundant peptides are so scarce or labile that they are likely‘overlooked’during the characterization effort.Here,we present the biochemical characterization and druggability improvement of an unprecedented minor fungal RiPP(ribosomally synthesized and post-translationally modified peptide),named acalitide,by taking the relevant advantages of metabolomics approach and disulfide-bridged substructure which is more frequently imprinted in the marketed peptide drug molecules.Acalitide is biosynthetically unique in the macrotricyclization via two disulfide bridges and a protease(AcaB)-catalyzed lactamization of AcaA,an unprecedented precursor peptide.Such a biosynthetic logic was successfully re-edited for its sample supply renewal to facilitate the identification of the in vitro and in vivo antiparkinsonian efficacy of acalitide which was further confirmed safe and rendered brain-targetable by the liposome encapsulation strategy.Taken together,the work updates the mining strategy and biosynthetic complexity of RiPPs to unravel an antiparkinsonian drug candidate valuable for combating Parkinson’s disease that is globally prevailing in an alarming manner.

关键词： Fungal RiPPs Biosynthesis Macrocyclic peptide Acalitide Antiparkinsonian

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

Symbionts, a promising source of bioactive natural products

引用

Science China Chemistry 2015年第7期58卷 1097-1109页

作者： Xuan Zhang Wei Wei renxiang tan State Key Laboratory of Pharmaceutical Biotechnology College of Life Science Nanjing University

Symbionts are microorganisms residing in multicellular hosts(e.g., plants and animals), and they have been witnessed to be a rich source of diverse functional molecules. This review describes structures and biological activities of symbiont-derived secondary metabolites commonly referred to as "natural products", and highlights that symbiotic microbes represent an underexplored reservoir of natural products with unique scaffolds and promising significance in managing human healthcare and agricultural production.

关键词：天然产物生物活性共生体次生代谢产物功能分子天然产品医疗保健微生物

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

Cytotoxic and antibacterial polyketide-indole hybrids synthesized from indole-3-carbinol by Daldinia eschscholzii

引用

Acta Pharmaceutica Sinica B 2019年第2期9卷 369-380页

作者： Liping Lin Nan Jiang Huimin Wu Yaning Mei Jie Yang renxiang tan State Key Laboratory Cultivation Base for TCM Quality and Efficacy Nanjing University of Chinese Medicine State Key Laboratory of Pharmaceutical Biotechnology Nanjing University School of Pharmacy Nanjing Medical University Department of Clinical Laboratory the First Affiliated Hospital of Nanjing Medical University Jiangsu Province Academy of Traditional Chinese Medicine

Two skeletally undescribed polyketide-indole hybrids(PIHs), named indolchromins A and B,were generated from indole-3-carbinol(I3 C) in the fungal culture(Daldinia eschscholzii). The indolchromin structures were elucidated mainly by their 1 D and 2 D NMR spectra with the former confirmed by the single-crystal X-ray crystallographic analysis. Each indolchromin alkaloid was chirally separated into four isomers, whose absolute configurations were assigned by comparing the recorded circular dichroism(CD) spectra with the electronic CD(ECD) curves computed for all optional stereoisomers. Furthermore, the indolchromin construction pathways in fungal culture were clarified through enzyme inhibition, precursor feeding experiment, and energy calculation. The cascade reactions,including decarboxylative Claisen condensation catalyzed by 8-amino-7-oxononanoate synthase(AONS),C(sp3)-H activation, double bond migration, and Michael addition, all undergone compatibly during the fungal cultivation. In an MIC range of 1.3–8.6 μmol/L,(2 S,4 R)-and(2 R,4 S)-indolchromin A and(2 R,4 S)-indolchromin B are inhibitory against Clostridium perfringens, Clostridium difficile, Veillonella sp.,Bacteroides fragilis, and Streptococcus pyogenes.(2 R,4 S)-Indolchromin A and(2 S,4 S)-indolchromin B were cytotoxic against the human breast cancer cell line MDA-MB-231 with IC50 values of 27.9 and131.2 nmol/L, respectively, with the former additionally active against another human breast cancer cell line MCF-7(IC_(50)94.4 nmol/L).

关键词： Polyketide-indole hybrids Indole-3-carbinol Daldinia eschscholzii 8-Amino-7-oxononanoate synthase Decarboxylative Claisen condensation Antibacterial Anticancer

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

Anti-inflammatory spirobisnaphthalene natural products from a plant-derived endophytic fungus Edenia gomezpompae

引用

Chinese Chemical Letters 2020年第6期31卷 1406-1409,F0002页

作者： Yingzi tan Zhikai Guo Mengyue Zhu Jing Shi Wei Li Ruihua Jiao renxiang tan Huiming Ge State Key Laboratory of Pharmaceutical Biotechnology Institute of Functional BiomoleculesSchool of Life SciencesNanjing UniversityNanjing 210023China Hainan Key Laboratory of Tropical Microbe Resources Institute of Tropical Bioscience and BiotechnologyChinese Academy of Tropical Agricultural SciencesHaikou 571101China State Key Laboratory Cultivation Base for TCM Quality and Efficacy Nanjing University of Chinese MedicineNanjing 210023China Hainan Academy of Tropical Agricultural Resource Chinese Academy of Tropical Agricultural SciencesHaikou 571101China

Spirobisnaphthalenes comprise a relatively rare family of natural products that are normally isolated from fungi and occasionally from plants.Here we reported the discovery of seven new preussomerintype spirobisnaphthalenes,preussomerins YT1-YT7(1-7),and seven known ones(8-14),from the endophytic fungus Edenia gomezpompae,enriching the structural diversity of this family of natural products.Their structures were established by 1 D and 2 D NMR spectroscopy,HRESIMS analysis and comparison with previously reported compounds,with the absolute configurations of compounds 1 and2 being further confirmed by single-crystal X-ray diffraction using Cu Ka radiation.The antiinflammatory activities of all isolates were assessed by measuring the production of NO in LPS-induced RAW264.7 macrophage cells.Among them,compounds 8 and 13 exhibited potent inhibitory activities on the production of NO,with IC50 values of 2.61 and 1.32μmol/L,respectively.

关键词： Endophytic fungus Spirobisnaphthalene natural products Preussomerin-type Structure elucidation Anti-inflammatory activity

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

Identification of highly efficacious PROTACs targeting BRD4 against acute myeloid leukemia:Design,synthesis,and biological evaluations

引用

Chinese Chemical Letters 2023年第6期34卷 426-431页

作者： Aiping Chen Yue Zhong Yunxiao Liu Zhancheng Xie Hanyu Wu Wei Shi Wenlong Huang renxiang tan Hai Qian College of Pharmacy Nanjing University of Chinese MedicineNanjing 210023China Center of Drug Discovery State Key Laboratory of Natural MedicinesChina Pharmaceutical UniversityNanjing 210009China Jiangsu Key Laboratory of Drug Discovery for Metabolic Disease China Pharmaceutical UniversityNanjing 210009China

The abnormal activation of BRD4 accelerates the progression of acute myeloid leukemia(AML),developing more precise therapeutics to intervene BRD4 promise to be an excellent opportunity to avoid current limitations of chemotherapy in clinic.Herein,a range of small-molecule PROTACs with the privileged 8-methyl-pyrrolo[1,2-a]pyrazin-1(2H)-one scaffold were rationally designed,which harbored different carbon or ethylenedioxy chains to degrade BRD4 mediated by the E3 ubiquitin ligase CRBN.Among them,the most potential B24 exhibited remarkable BRD4 degradation and excellent anti-proliferative activities in MV4-11 cells,with values of DC_(50)and IC_(50)for 0.75 nmol/L and 0.4 nmol/L,respectively,which were better than the BRD4 inhibitor(+)-JQ-1.Notably,this compound could time-dependently degrade the target protein in the BRD4-,CRBN-,and proteasome-dependent manner.Besides,B24 dramatically decreased the level of proto-oncogene c-Myc,and induced cell apoptosis by arresting the cell cycle in G0/G1 phase,down-regulating Bcl-2 and up-regulating Bax to amplify apoptotic effectors.This proof-of-concept study also highlighted the feasibility of BRD4-based PROTACs as a more powerful strategy against AML.

关键词： Acute myeloid leukemia BRD4 PROTACs Protein degradation Apoptosis

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

Chartrenoline, a novel alkaloid isolated from a marine Streptomyces chartreusis NA02069

引用

Chinese Chemical Letters 2019年第1期30卷 44-46页

作者： Chengli Liu Chenglong Yang Yingjie Zeng Jing Shi Lingyu Li Wei Li Ruihua Jiao renxiang tan Huiming Ge State Key Laboratory of Pharmaceutical Biotechnology Institute of Functional Biomolecues School of Life Sciences Nanjing University

A novel alkaloid, chartrenoline(1), featuring an unusual 6/6/5/5-tetracyclic nucleus, was isolated from a marine Streptomyces chartreusis NA02069. The structure of 1 including its absolute configurations was established by extensive analyses of its high resolution mass, NMR and single-crystal X-ray diffraction data. A plausible biosynthetic pathway for chartrenoline(1) is proposed.

关键词： Alkaloid Chartrenoline Streptomyces chartreusis 6/6/5/5-Tetracyclic nucleus Marine-derived microorganism

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

基于改进YOLOv5的无人机目标识别方法

引用

现代信息科技 2024年第3期8卷 84-88页

作者：魏麟何峻毅谭任翔彭俊榕中国民用航空飞行学院飞行技术学院四川德阳618307 中国民用航空飞行学院航空电子电气学院四川德阳618307

据统计资料显示,截至2017年全球已经售出无人机达300万架。无人机具有体积小、成本低、数量大等特点,这也随之引起了一系列的安全问题,对公共安全造成了严重威胁。传统的对无人机的识别方法主要有雷达探测、声波探测等。在分析了传统识... 详细信息

据统计资料显示,截至2017年全球已经售出无人机达300万架。无人机具有体积小、成本低、数量大等特点,这也随之引起了一系列的安全问题,对公共安全造成了严重威胁。传统的对无人机的识别方法主要有雷达探测、声波探测等。在分析了传统识别方法的劣势后,提出了基于改进YOLOv5的无人机识别方法,在原始YOLOv5模型的基础上添加CBAM注意力机制,以增强目标特征提取的能力,增强网络模型性能。并可引入DeepSORT跟踪算法,为无人机的跟踪提供检测响应。经过测试集测试,改进后的模型较原始模型的精确度提升了5.24%,基本满足识别要求。

关键词：无人机目标识别 YOLOv5 CBAM DeepSORT

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 acidic polysaccharide with xylose branches from Porphyra yezoensis

引用

Chinese Science Bulletin 2001年第3期46卷 207-210页

作者： ZHANG Weiyun CHEN Hao WANG Shuijuan XIA Zhonghao FEI Xiugeng tan renxiang Institute of Functional Biomolecules State Key Laboratory of Pharmaceutical BiotechnologySchool of Life SciencesNanjing UniversityNanjing 210093China Experimental Marine Biology Laboratory Institute of OceanologyChinese Academy of SciencesQingdao 266071China

An acidic polysaccharide (PY3) was isolated from the hot water extract of the red algae Porphyra yezoensis by successive column chromatographies over DEAE-cellulose and Sephadex G-200. PY3 with an average molecular weight of 1.8×105 was demonstrated to be composed of galactose (Gal), 3,6-anhydrogalactose (3,6-AnGal), 6-OSO3-galactose (6-OSO3-Gal) and xylose (Xyl) in an approximate molar ratio of 25:15:10:1. In view of Smith degradation and me-thylation and on the basis of spectral evidence including those of IR, GC, GC-MS, and 1H and 13C NMR, the most probable repeating unit of PY3 could be proposed as [(1-3)β-D-Gal(1- 4)α-L-3,6-AnGal]3-[1-3)β-D-Gal(1-4)α-L-6-OSO3-Gal]2 with a xylose moiety at the C6 of one of every twenty-five β-D-Gal residues. To our knowledge, PY3 was shown to be the first porphyran possessing occasional xylose branches.

关键词： Porphyra yezoensis acidic polysaccharide structure elucidation.

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

Functionalized lipid nanoparticles modulate the blood-brain barrier and eliminate α-synuclein to repair dopamine neurons

引用

Asian Journal of Pharmaceutical Sciences 2024年第2期19卷 120-135页

作者： Xiaomei Wu renxiang Yuan Yichong Xu Kai Wang Hong Yuan Tingting Meng Fuqiang Hu Department of Pharmacy Ruijin HospitalSchool of MedicineShanghai Jiaotong UniversityShanghai 200000China College of Pharmaceutical Science Zhejiang UniversityHangzhou 310058China Jinhua Institute of Zhejiang University Jinhua 321299China

The challenge in the clinical treatment of Parkinson's disease lies in the lack of disease-modifying therapies that can halt or slow down the progression. Peptide drugs, such as exenatide (Exe), with potential disease-modifying efficacy, have difficulty in crossing the blood-brain barrier (BBB) due to their large molecular weight. Herein, we fabricate multi-functionalized lipid nanoparticles (LNP) Lpc-BoSA/CSO with BBB targeting, permeability-increasing and responsive release functions. Borneol is chemically bonded with stearic acid and, as one of the components of Lpc-BoSA/CSO, is used to increase BBB permeability. Immunofluorescence results of brain tissue of 15-month-old C57BL/6 mice show that Lpc-BoSA/CSO disperses across the BBB into brain parenchyma, and the amount is 4.21 times greater than that of conventional LNP. Motor symptoms of mice in Lpc-BoSA/CSO-Exe group are significantly improved, and the content of dopamine is 1.85 times (substantia nigra compacta) and 1.49 times (striatum) that of PD mice. α-Synuclein expression and Lewy bodies deposition are reduced to 51.85% and 44.72% of PD mice, respectively. Immunohistochemical mechanism studies show AKT expression in Lpc-BoSA/CSO-Exe is 4.23 times that of PD mice and GSK-3β expression is reduced to 18.41%. Lpc-BoSA/CSO-Exe could reduce the production of α-synuclein and Lewy bodies through AKT/GSK-3β pathway, and effectively prevent the progressive deterioration of Parkinson's disease. In summary, Lpc-BoSA/CSO-Exe increases the entry of exenatide into brain and promotes its clinical application for Parkinson's disease therapy.

关键词： Blood-brain barrier Lipid nanoparticles Brain delivery facilitation α-Symuclein Parkinson's disease

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Acatulides A-G,neuroprotective macrolides from Acaulium album H-JQSF

引用

Chinese Chemical Letters 2024年第3期35卷 379-383页

作者： Zhi-Wu Tong Ting-Ting Wang Pei Yang Jia-Lin Sun Chen-Peng Zhang Salman Khan Xin-Cun Wang Rui-Hua Jiao Hui-Ming Ge Wen-Ying Zhuang Gang Hu Ren Xiang tan State Key Laboratory of Pharmaceutical Biotechnology Institute of Functional BiomoleculesNanjing UniversityNanjing 210023China State Key Laboratory Cultivation Base for TCM Quality and Efficacy Nanjing University of Chinese MedicineNanjing 210023China Insitute of Microbiology Chinese Academy of SciencesBeijing 100101China

Fungal symbionts co-evolve with hosts and microbial co-inhabitants to acquire an unpredictable potential for producing novel bioactive metabolites,but the knowledge about the topic remains patchy and superficial.Here we present the chemical characterization of acatulides A-G(1-7)as architecturally unprecedented macrolides from the solid-state culture of Acaulium album H-JQSF,an arthropod-associated fungus.The acatulide structures were elucidated by spectroscopic analysis,modified Mosher's method and single-crystal X-ray diffraction.The plausible biosynthetic pathways for compounds 1-4 are proposed.Interestingly,acatulides B-D(2-4)and G(7)were demonstrated to be neuroprotective against the 1-methyl-4-phenylpyridinium(MPP+)-induced damage to SH-SY5Y cells and nematode Caenorhabditis elegans(C.elegans).

关键词： Acaulium album Macrolides Acatulides A–G Mosher’s method Neuroprotective

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：