魏春英
(1)核酸的多态性;(2)选择性识别不同结构、构象核酸探针分子的设计、合成;(3)基于G-quadruplex DNA新靶标的抗癌新药的设计、合成,生物活性及其作用机理研究。
个性化签名
- 姓名:魏春英
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学术头衔:
博士生导师
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学科领域:
无机化学
- 研究兴趣:(1)核酸的多态性;(2)选择性识别不同结构、构象核酸探针分子的设计、合成;(3)基于G-quadruplex DNA新靶标的抗癌新药的设计、合成,生物活性及其作用机理研究。
魏春英,女,1970年6月出生。博士,教授,博士生导师。1993年毕业于山西大学化学系,获理学学士学位,1996年获山西大学理学硕士学位,2002年获山西大学理学博士学位。曾在日本Konan University和中科院大连化学物理研究所做博士后研究,在国内外重要期刊发表论文30余篇,主持多项国家和山西省自然科学基金项目。
目前主要研究方向为生物无机化学和化学生物学。
研究兴趣主要为:
(1)核酸的多态性;
(2)选择性识别不同结构、构象核酸探针分子的设计、合成;
(3)基于G-quadruplex DNA新靶标的抗癌新药的设计、合成,生物活性及其作用机理研究。
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成果数
7
【期刊论文】Spectroscopic study on the binding of porphyrins to (G4T4G4)4 parallel G-quadruplex
魏春英, Chunying Wei*, Junhong Wang, Meiying Zhang
Biophysical Chemistry 148(2010)51-55,-0001,():
-1年11月30日
The binding mode and stoichiometry of the cationic porphyrin TMPyP4 to G-quadruplex structure are still controversial to date, mainly due to the intricate polymorphism of G-rich sequences in the different conditions of solution. Here in the presence of the molecular crowding agent PEG, the binding interaction of TMPyP4 and another porphyrin derivative TPrPyP4 with four-stranded parallel (G4T4G4)4 G-quadruplex was studied systematically using circular dichroism, visible absorption titration, and steady-state and timeresolved fluorescence spectroscopies. The results show that each (G4T4G4)4 molecule is able to bind four TMPyP4 or TPrPyP4 molecules. Two types of independent and nonequivalent binding sites with the higher and lower binding affinity are confirmed, and the stronger and weaker binding constants are 2.74×108 and 8.21×105 M−1 for (G4T4G4)4-TMPyP4, 2.05×108 and 1.05×106 M−1 for (G4T4G4)4-TPrPyP4, respectively. The two porphyrin molecules stack on the two ends of G-quadruplex with the higher binding affinity, another two porphyrins bind weakly to the two external grooves.
Molecular crowding, G-quadruplexes, Interaction, Porphyrin, Antitumor drugs, Spectroscopy
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魏春英, Guoqing Jia, †, ‡ Zhaochi Feng, † Chunying Wei, § Jun Zhou, ‡ Xiuli Wang, ‡ and Can Li*
J. Phys. Chem. B 2009, 113, 16237-16245,-0001,():
-1年11月30日
Understanding the nature of the interaction between small molecules and G-quadruplex DNA is crucial for the development of novel anticancer drugs. In this paper, we present the first data on time-resolved fluorescence anisotropy study on the interaction between a water-soluble cationic porphyrin H2TMPyP4 and four distinct G-quadruplex DNAs, that is, AG3(T2AG3)3, thrombin-binding aptamer (TBA), (G4T4G4)2, and (TG4T)4. The anisotropy decay curves show the monoexponential for free H2TMPyP4 and the biexponential upon binding to the excess amount of G-quadruplex DNAs. The biexponential anisotropy decay can be well interpreted using a wobbling-in-the-cone model. The orientational diffusion of the bound H2TMPyP4 is initially restricted to a limited cone angle within the G-quadruplex DNAs, and then an overall orientational relaxation of the G-quadruplex DNA-H2TMPyP4 complexes occurs in a longer time scale. It was found that the dynamics of the restricted internal rotation of bound H2TMPyP4 strongly depends on the ending structures of the G-quadruplex DNAs. According to the order parameter (Q) calculated from the wobbling-in-the-cone model, we deduce that the degree of restriction around the bound H2TMPyP4 follows the order of TBA>(TG4T)4>AG3(T2AG3)3>(G4T4G4)2. Especially, based on the maximum order parameter (Q) of bound H2TMPyP4 within TBA, a new sandwich-type binding mode for TBA-H2TMPyP4 complex was proposed in which both terminal G-quartet and T•T base pair stack on the porphyrin ring through π-π interaction. This study thus provides a new insight into the interaction between G-quadruplex DNAs and H2TMPyP4.
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魏春英, Jun Zhou a, b, Chunying Wei a, c, Guoqing Jia a, Xiuli Wang a, Zhaochi Feng a, Can Li a, *
Biochimie 91(2009)1104-1111,-0001,():
-1年11月30日
The structural interconversion between the G-quadruplex and duplex in vivo is an important subject. In the present study, we used human telomeric DNA duplex composed of GGG(TTAGGG)3/CCC(TAACCC)3 as a model system to investigate its properties under near physiological conditions by spectroscopic methods. Circular dichroism and fluorescence spectra demonstrated that G-quadruplex structure can be formed from duplex at near physiological pH (pH 7.4), salt concentration (150 mM Kþ), and temperature (37℃) in the presence of molecular crowding agent PEG (400 g/l), whereas the G-quadruplex structure cannot be formed at 25 C in buffer containing 150 mM Kþ in the presence of PEG. It is found that the formation rate of G-quadruplex structure depends on the temperature and the concentrations of both PEG and Kþ. This work suggests that human telomeric G-quadruplex structure may be potentially formed from Watson–Crick duplex in vivo.
G-quadruplex, Duplex, Structural interconversion, Molecular crowding
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魏春英, Chunying Wei a, *, Lihua Wang a, Guoqing Jia b, Jun Zhou b, Gaoyi Han a, Can Li b
Biophysical Chemistry 143(2009)79-84,-0001,():
-1年11月30日
Interactions of 5,10,15,20-Tetrakis(N-methylpyridinium-4-yl)-21H,23H-porphyrin (TMPyP4) and 5,10,15,20-Tetrakis(N-propylpyridinium-4-yl)-21H, 23H-porphyrin (TPrPyP4) with the parallel four-stranded (TG4T)4 G-quadruplex DNA in 100 mM K+-containing buffer were studied using circular dichroism (CD) spectroscopy, visible absorption titration, and steady and time-resolved fluorescence spectroscopies. The results show that the binding stoichiometric ratios of both TMPyP4 and TPrPyP4 to (TG4T)4 are 3:1. Two types of independent and nonequivalent binding sites with the higher and lower binding affinities are confirmed, and the stronger and weaker binding constants are 9.44×107 and 6.94×105 M−1 for (TG4T)4-TMPyP4 complex, 7.86×107 and 6.35×105M−1 for (TG4T)4-TPrPyP4 complex, respectively. For both TMPyP4-(TG4T)4 and TPrPyP4–(TG4T)4 complexes, one porphyrin molecule stacks on the one end of G-quadruplex with the higher binding affinity, another two porphyrins bind weakly to the two external grooves. The size of cation side arms around porphyrin core almost fails to affect the binding mode, stoichiometry and affinity of porphyrin to (TG4T)4 G-quadruplex in 100 mM K+-containing buffer.
Binding modes, G-quadruplexes, Interaction, Porphyrin, Spectroscopy
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【期刊论文】Structural transition from the random coil to quadruplex of AG3(T2AG3)3 induced by Zn2+
魏春英, Chunying Wei a, *, Qian Tang b, Can Li c
Biophysical Chemistry 132(2008)110-113,-0001,():
-1年11月30日
Structures of G-quadruplex DNAs can be typically stabilized by monovalent cations such as K+, Na+. Some divalent and trivalent cations, such as Sr2+, Pb2+, Tb3+ and Eu3+, can also induce the formation of G-quadruplex DNA. Here we show that Zn2+ can induce the human telomeric sequence AG3(T2AG3)3 to fold the G-quadruplex structure by UV absorbance difference spectra and circular dichroism (CD) spectroscopy. At micromolar concentrations, the Zn2+-induced changes in the UV absorbance difference spectra and CD spectra are the characteristics of antiparallel G-quadruplexes although the long wavelength CD maximum is around 285 nm rather than the typical value of 295 nm. The binding stoichometry of Zn2+ per one AG3(T2AG3)3 molecule is four. To our knowledge, the structural transition of human telomeric sequence induced by Zn2+ was observed for the first time.
Zn2+, , G-quadruplexes, Spectroscopy, Structural transitions
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魏春英, a State Key Laboratory of Catalysis, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian , China b Graduate School of Chinese Academy of Sciences, Beijing , China c Bioengineering College, Dalian University, China
Biophysical Chemistry 136(2008)124-127,-0001,():
-1年11月30日
The structure polymorphism of human telomeric G-quadruplex (ht-quadruplex) is currently an important topic but remains controversy. Here, we present study of the ht-quadruplex under the cation-deficient but molecular crowding conditions by circular dichroism (CD), microchip electrophoresis (MCE) and UV-melting experiments. Our results show that with concentration increasing of poly(ethylene glycol) (PEG), the structural transition of ht-quadruplex occurs accompanied by structural compaction and enhanced stabilization, which may be caused by excluded volume effect. This work also demonstrates that htquadruplex can be well assembled without cations and the structure of ht-quadruplex is actually very complex in vivo.
Human telomeric G-quadruplex, Molecular crowding, Excluded volume effect, Structural transition, Compaction
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魏春英, Chunying Wei a, Bo Songb, Jingli Yuan b, Zhaochi Feng a, Guoqing Jia a, Can Li a, ∗
Journal of Photochemistry and Photobiology A: Chemistry 189(2007)39-45,-0001,():
-1年11月30日
In connection with the chemical modification of protein, the photooxidation of histidine (His), tryptophan (Trp) and carnosine by singlet oxygen (1O2) is investigated by a Eu3+ luminescence probeATTA-Eu3+ andUVRaman spectroscopy under physiological conditions (pH 7.5). The solutions containing both the luminescence probe ATTA-Eu3+(1×10−5 M) and the different concentration of the biological targets His, Trp or carnosine were irradiated by a tungsten lamp in the presence of 1O2 photosensitizer H2TMPyP4 (1×10−5 M), the luminescence intensity of the Eu3+ complex probe decreases linearly with increasing the concentration of the biological target. The reaction rate constants of 1O2 with His, Trp and carnosine were calculated to be 3.2×108, 7.7×107 and 1.3×108M−1 s−1, respectively. The results suggest that the luminescence probe ATTA-Eu3+ can be used for detecting the reactions of 1O2 with the biological targets quantitatively under physiological conditions. UV Raman spectroscopy probes the structural changes of these biological targets after reaction with 1O2, indicating that peroxides are main species for the reaction of Trp although the products decomposed by peroxides are main forms for that of His in a buffer solution. The imidazole ring of carnosine is the target of 1O2, and the peptide bond is almost intact after reaction with 1O2.
Singlet oxygen, Carnosine, Amino acids, Spectroscopy
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