杨晓达
(1)无机离子调节细胞生命过程的化学基础;(2)疾病相关的金属(铜、铁)代谢;(3)无机药物(抗糖尿病钒化合物)的ADMET研究。
个性化签名
- 姓名:杨晓达
- 目前身份:
- 担任导师情况:
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学术头衔:
博士生导师
- 职称:-
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学科领域:
无机化学
- 研究兴趣:(1)无机离子调节细胞生命过程的化学基础;(2)疾病相关的金属(铜、铁)代谢;(3)无机药物(抗糖尿病钒化合物)的ADMET研究。
杨晓达生于1966年;1988年于北京大学获理学学士学位;1991年于北京大学获理学硕士学位;1994年于北京大学获理学博士学位;1994-1997年于北京医科大学药学院从事博士后研究;1997-2000年在美国堪萨斯大学药学院药物化学系从事博士后研究。2000回国工作。 曾经从事稀土生物化学、时间分辨荧光免疫分析、酶生物化学和结构并基于机理的药物设计。目前从事生物无机化学和无机药物化学研究,研究方向包括:(1)无机离子调节细胞生命过程的化学基础;(2)疾病相关的金属(铜、铁)代谢;(3)无机药物(抗糖尿病钒化合物)的ADMET研究。 目前教授课程包括:(1)医学基础化学;(2)无机药学理论和方法;(3)酶化学和基于机理的药物设计;(4)现代ADMET研究方法;(5)化学生物学专业英语。
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杨晓达
大学化学,19(5)14~17,-0001,():
-1年11月30日
探讨与生命科学相关专业的化学基础课程为适应新形势的发展需要应该进行的调整与改革。
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杨晓达, Yang Xiaoda Chang Werdoao Ci Yunxiang
化学进展,1995,7(2)83~97,-0001,():
-1年11月30日
本文首先从试剂分析的观点对免疫分析的原理进行了论述,对抗体作为分析试剂进行了评价并且总结了标记免疫分析的三种方式和四个环节;其次,对免疫分析的现状作了综述,并评述了当代免疫分析的五个热点:基因工程抗体,生物素一亲合素多重标记体系,时间分辨荧光免疫分析,多组分免疫分析和自动化免疫分析;最后,对免疫分析的发展趋势作了讨论。
免疫分析抗体 基因工程抗体 多重标记 时间分辨荧光免疫分析
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杨晓达, Yang Xiaoda* Yang Xiaogai
化学进展,2004,14(4)273~278,-0001,():
-1年11月30日
无机物的吸收、分配、代谢和排除以及毒性(ADM EöT ox)研究在药物和毒物研究中非常重要。近年来发展的在细胞层次上应用高通量和计算机等技术系统探索药物先导化合物的ADM EöT ox 发展迅速。金属和其它无机化合物的ADM EöT ox 研究在国内外都还是一个新兴的、具有广阔发展前途的跨学科研究领域。本文综述了国内外对于铁和铜以及稀土等金属的化合物的ADM EöT ox 研究结果。提出一些应该开展的工作和有待解决的问题
无机药物 ADM EöT ox 药物动力学 药物化学 金属离子
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杨晓达, Yang Xiaoda Zhang Tianlan Wang Kui
化学进展,2004,16(5)836~841,-0001,():
-1年11月30日
在探索生命奥秘的过程中,生物无机化学研究由分子层次上升到细胞层次是一个必然的趋势,也是解决实际问题的需要,细胞无机化学研究在细胞生命体系中的无机化学反应和探索无机物对生命过程调节或干预的作用和机理,是探索生命体系复杂性研究的重要部分。细胞是保留完整生命活动特征的最小单位,存在周期、分化和受激等状态的不同。从化学的观点,细胞是一个严密设计的分子有序组装体,为一个多靶分子系统,细胞应答表现为由相关反应组合成的复杂过程。细胞无机化学研究包括无机物种在细胞膜上的结合和随后发生的膜结构和功能改变、跨细胞膜和跨生物组织屏障的转运和细胞代谢、细胞中无机化学反应同细胞信号系统的偶联、无机离子与自由基的相互代谢关系以及细胞-无机物固相的相互作用等方面。本文对当前细胞无机化学研究的重点问题进行了讨论。
细胞无机化学 细胞 信号传导 无机物 自由基
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【期刊论文】Cell Responses to Lanthanides and Potential Pharmacological Actions of Lanthanides
杨晓达, Kui Wang, Yi Cheng, Xiaoda Yang, and Rongchang Li
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-1年11月30日
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【期刊论文】The Permeability and Cytotoxicity of Insulin-Mimetic Vanadium Compounds
杨晓达, Xiao-Gai Yang, Xiao-Da Yang, , Lan Yuan, Kui Wang, and Debbie C. Crans
Pharmaceutical Research, Vol. 21, No.6, June 2004,-0001,():
-1年11月30日
Purpose. The aim of this study was to investigate the mechanism of permeation and cytotoxicity of vanadium compounds, [VO(acac)2], [VO(ma)2], and vanadate. Methods. Absorptive transport were carried out in Caco-2 monolayers grown on transwell inserts. Vanadium was quantified using inductively coupled plasma atomic emission spectrometry (ICP-AES). The change of Caco-2 cells in the microvilli morphology and F-actin structure was visualized by transmission electron microscopy and confocal laser scanning microscopy. Results. The three vanadium compounds were taken up by Caco-2 cells via simple passive diffusion. [VO(acac)2] were mainly transcellularly transported and exhibited the highest apparent permeabilty coefficients (8.2 × 10−6 cm-1). The cell accumulation of [VO(acac)2] was found to be greater than that of [VO(ma)2], and vanadate caused much less accumulation than the other two compounds. Vanadium compounds induced intracellular reactive oxygen species, reduced the transepithelial electric resistance, caused morphological change in microvilli, and led to different perturbation of F-actin structure. Conclusions. The three compounds exhibited different permeability due to different diffusion process and cellular uptake. The toxicity of vanadium complexes on Caco-2 monolayer involved F-actin-related change of tight junction and impairment of microvilli. The toxicity was also related to elevated intracellular reactive oxygen species (ROS) and their cellular accumulation.
Caco-2 cells, confocal laser scanning microscopy, cytotoxicity, F-actin, vanadium compounds.,
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杨晓达, Yun-Xiang Ci*, Xiao-Da Yang, Wen-Bao Chang
Journal of Immunological Methods 179(1995)233-241,-0001,():
-1年11月30日
Five β-diketone derivative were studied for multiple labelling of protcis. The labclled proteins were characterized by absorption and fluorescence measuremcnts. It Was found that proteins labelled with chlorosulfonyl thenoyltrifluoroacetone (CTTA) were able to form highly fluorescent complexes with Eu3+ which exhibite4d prolonged fluorescence wheresas the Eu3+ complex of hydrolyxed CTTA exhibited almost no fluorescence, and so unreacted ligand gave no background signal in immmunooassays even if it was not removed from the labelled reagent. The cffect of labelling on the biological activity of albumin and polycolonal antibody was studied and it was also shown that the new probe could be used in time-resolved fluorescence immunoassays.
β-Diketone, Multiple labelling, Time-resolved fluoroommunoassay
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【期刊论文】La3+-Promoted Proliferation Is Interconnected with Apoptosis in NIH 3T3 Cells
杨晓达, Siwang Yu, Lan Yuan, Xiaoda Yang*, , Kui Wang, Zhong-ming Qian*
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-1年11月30日
Lanthanum ion (La3+) has been reported to affect proliferation or apoptosis of different cells. In the present study, La3+ was confirmed to promote both proliferation and apoptosis of NIH 3T3 cells at the same concentrations. La3+ was shown to promote proliferation by helping the cells to pass through the G1/S restriction point and enter S phase, however, the proliferating cells induced by incubation with La3+ eventually underwent apoptosis. The proliferation and apoptosis of NIH 3T3 cells induced by La3+ were well correlated with cell-cycle alterations. La3+ caused the phosphorylation of extracellular signal-regulated kinase (ERK) 1/2; while inhibition of ERK phosphorylation by 2'-amino-3'-methoxyflavone (PD98059) suppressed both proliferation and apoptosis induced by La3+. Based on the above experimental results, we postulated that La3+-promoted proliferation of NIH 3T3 cells could be interconnected with the cell apoptosis, possibly through cell-cycle machinery. Our results thus support the recent hypothesis that proliferation and apoptosis of cell are intrinsically coordinated.
La3+, ,, proliferation,, apoptosis,, cell-cycle,, ERK
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杨晓达, Jian Hu, ‡ Xin Jia, *, § Qin Li, § Xiaoda Yang, ‡ and Kui Wang‡, §
Biochemistry 2004, 43, 2688-2698,-0001,():
-1年11月30日
Binding of La3+ to calmodulin (CaM) and its effects on the complexes of CaM and CaMbinding peptide, polistes mastoparan (Mas), were investigated by nuclear magnetic resonance (NMR) spectroscopy, fluorescence and circular dichroism spectroscopy, and by the fluorescence stopped-flow method. The four binding sites of La3+ on CaM were identified as the same as the binding sites of Ca2+ on CaM through NMR titration of La3+ to uniformly 15N-labeled CaM. La3+ showed a slightly higher affinity to the binding sites on the N-terminal domain of CaM than that to the C-terminal. Large differences between the 1H-15N heteronuclear single quantum coherence (HSQC) spectra of Ca4CaM and La4CaM suggest conformational differences between the two complexes. Fluorescence and CD spectra also exhibited structural differences. In the presence of Ca2+ and La3+, a hybrid complex, Ca2La2CaM, was formed, and the binding of La3+ to the N-terminal domain of CaM seemed preferable over binding to the C-terminal domain. Through fluorescence titration, it was shown that La4CaM and Ca2La2CaM had similar affinities to Mas as Ca4CaM. Fluorescence stopped-flow experiments showed that the dissociation rate of La3+ from the C-terminal domain of CaM was higher than that from the N-terminal. However, in the presence of Mas, the dissociation rate of La3+ decreased and the dissociation processes from both global domains were indistinguishable. In addition, compared with the case of Ca4CaM-Mas, the slower dissociations of Mas from La4CaM-Mas and Ca2La2CaM-Mas complexes indicate that in the presence of La3+, the CaM-Mas complex became kinetically inert. A possible role of La3+ in the Ca2+-CaM-dependent pathway is discussed.
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【期刊论文】膜分子通道揭示了生命现象的化学机制——2003年诺贝尔化学奖简介
杨晓达, 李娜*, 杨晓达**
大学化学,2004,19(1):16~21,-0001,():
-1年11月30日
2003年度的诺贝尔化学奖授予洛克菲勒大学的Roderick MacKinnon博士和约翰斯·霍普金斯大学的Peter Agre博士,以表彰他们在细胞膜水分子通道和离子通道方面所做的开创性工作。本文简介2003年诺贝尔化学奖获得者及其工作。
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