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High activity of Mj HSP16.5 under acidic condition

Science China Chemistry 2009年第3期52卷 325-331页

作者： WANG Zheng cao aoneng LAI LuHua Beijing National Laboratory for Molecular Sciences and State Key Laboratory of Structural Chemistry for Stable and Unstable SpeciesCollege of Chemistry and Molecular EngineeringPeking UniversityBeijing 100871China Institute of Nanochemistry and Nanobiology Shanghai UniversityShanghai 200444China

Small heat shock proteins (sHSPs) exist ubiquitously among all organisms, with a variety of functions. All small heat shock proteins assemble into a native large oligomeric state containing 9–40 monomers. The sHSPs show chaperone-like activity to prevent the aggregation of nonnative proteins under stressful cellular conditions such as non-optimal temperatures, pH changes, osmotic pressure, and exposure to toxic chemicals. It was found that a common dimeric subunit of sHSPs might be the major active species, but whether the native large oligomeric state is only a storage state or a state crucial to its molecular chaperone activity is still under debate. The native large oligomeric state of the small heat shock protein from a hyperthermophilic methanarchaeon, Methanococcus jannaschii (Mj HSP 16.5), is a stable icositetramer, which is a symmetric hollow sphere that is very stable even at 85°C, and no small active subunit has been detected till now. Our results show that Mj sHSP 16.5 changes into small and active oligomeric state at pH 3, likely as octamers (average result) at 25°C, and dimers at 65°C. The dimer of Mj HSP 16.5 at pH 3.0 and 65°C is very active and efficient, even 7-fold more efficient than the high-temperature-activated icositetramer at neutral pH. Monomer exchange can be observed between dimers of Mj HSP 16.5 at pH 3.0 and 65°C. These results not only demonstrate that the icositetramer structure of Mj sHSP16.5 is not necessary for its molecular chaperone activity, but also suggest that Mj sHSP16.5 is a very efficient chaperone acting at high temperature and under the acidic condition. Even though it is not clear whether the native environment of Methanococcus jannaschii is acidic or not, given its ability to excrete acidic compounds, it is likely that Methanococcus jannaschii will encounter acidic internal or external environments at high temperature. Our results demonstrate that Mj HSP 16.5 may help Methanococcus jannaschii to survive better under tho

关键词： small heat shock protein chaperone Mj HSP16.5 dimer acidic folding aggregation

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Silica nanoparticle with a single His-tag for addressable functionalization, reversible assembly, and recycling

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Nano Research 2018年第5期11卷 2512-2522页

作者： Yuye cao Yangdong Cui Yu Yang Jie Hua Zheng-Mei song Haifang Wang Yuanfang Liu aoneng cao Institute of Nanochemistry and Nanobiology Shanghai University Shanghai 200444 China Beijing National Laboratory for Molecular Sciences College of Chemistry and Molecular Engineering Peking University Beijing 100871 China

For many biomedical and catalytic applications, such as encapsulation of proteins/enzymes in nanopartides （NPs）, it is preferable to have well-dispersed small NPs that are stable in solution and behave quasi-homogeneously. However, conventional liquid phase methods for small-NP synthesis and functionalization usually face great difficulties in separation/purification and recycling. In addition, controlling the orientation of proteins inside NPs is also a crucial issue to maximize the activity of the encapsulated proteins. Herein, we report a solid phase method to solve these problems. Using His-tagged proteins as cores, well-dispersed core-sheU silica NPs are facilely synthesized and functionalized in a column. The core His-tagged proteins are kept bound on the surface of the resIn beads in the column during the entire process, making the separation/purification of NPs and their precursors during the multiple-step process as simple as a few-minutes procedure of draining and washing the column. Each obtained silica NP has an adjustable eccentric core-shell structure with only one His-tag sticking out of the particle. This single His-tag on the surface of each NP not only makes it easy for addressable and stoichiometric functionalization of the NP but also provides an easy way to reversibly assemble NPs into dimers or be oriented on the surface of large particles. Notably, this solid phase approach also provides a versatile means to control the orientation of proteins inside NPs, and the His-tag makes it easy to recycle those well-dispersed small NPs.

关键词： His-tagged nanoparticle solid phase reversible assembly addressable functionalization protein orientation

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Stable isotope labeling of nanomaterials for biosafety evaluation and drug development

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Chinese Chemical Letters 2022年第7期33卷 3303-3314页

作者： Xue-Ling Chang Lingyun Chen Boning Liu Sheng-Tao Yang Haifang Wang aoneng cao Chunying Chen CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety Institute of High Energy PhysicsChinese Academy of SciencesBeijing 100049China Key Laboratory of Pollution Control Chemistry and Environmental Functional Materials for Qinghai-Tibet Plateau of the National Ethnic Affairs Commission School of Chemistry and EnvironmentSouthwest Minzu UniversityChengdu 610041China Institute of Nanochemistry and Nanobiology Shanghai UniversityShanghai 200444China CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety and CAS Center for Excellence in Nanoscience National Center for Nanoscience and Technology of Chinaand University of Chinese Academy of SciencesBeijing 100190China

Quantitative information,such as environmental migration,absorption,biodistribution,biotransformation,and elimination,is fundamental and essential for the nanosafety evaluations of *** to the complexity of biological and environmental systems,it is challenging to develop quantitative approaches and tools that could characterize intrinsic behaviors of nanomaterials in the *** isotopic tracers are ideal candidates to tune the physical properties of nanomaterials while preserving their chemical *** this review article,we summarized the stable isotope labeling methods of nanomaterials for evaluating their environmental and biological *** skeleton labeling protocols of carbon nanomaterials and metal/metal oxide nanoparticles were *** advantages and disadvantages of stable isotope labeling were discussed in comparison with other quantitative methods for *** quantitative information of nanomaterials in environmental and biological systems was summarized along with the biosafety *** benefits for drug development of nanomedicine were analyzed based on the targeting effects,persistent accumulation,and ***,the challenges and future perspectives of stable isotope labeling in nanoscience and nanotechnology were discussed.

关键词： Stable isotope labeling Quantification Carbon nanomaterials Metal oxide nanoparticles Nanotoxicity Biomedical effects

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Interaction of multi-walled carbon nanotubes and zinc ions enhances cytotoxicity of zinc ions

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Science China Chemistry 2016年第7期59卷 910-917页

作者： Lin Wang Jia-Hui Liu Zheng-Mei Song Yi-Xin Yang aoneng cao Yuanfang Liu Haifang Wang Institute of Nanochemistry and Nanobiology Shanghai University College of Life Science and Technology Beijing University of Chemical Technology Beijing National Laboratory for Molecular Sciences College of Chemistry and Molecular Engineering Peking University

More and more nanomaterials enter the environment along with their production, application and deposal. They may alter the biological effect of pollutants already existing in the real environment by different interactions. Therefore efforts should also be paid to investigate the combined toxicity of nanomaterials and pollutants. Herein, we studied the combined toxicity of oxi- dized multi-walled carbon nanotubes （O-MWCNTs） and zinc ions on ceils. It is found that cytotoxicity of the combined O-MWCNTs and zinc ions elevates significantly, compared with O-MWCNTs or zinc ions alone. This result comes from the assays of cell morphology, cell viability and proliferation, cell membrane integrity, mitochondrial membrane potential and cell apoptosis. Mechanism studies indicate that O-MWCNTs absorb zinc ions and form slight aggregation. These enhance remark- ably the cellular uptake of O-MWCNTs, and thus induce the death of cells by bringing in more zinc ions into cells. Our study indicates that the existence of nanomaterials could change the bioconsequence of other pollutants and emphasizes the im- portance of the combined toxicity research in the presence of nanomaterials.

关键词： carbon nanotube cytotoxicity zinc ion synergistic effect adsorption aggregation

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蛋白质结构的“限域下最低能量结构片段”假说与蛋白质进化的“石器时代”

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物理化学学报 2020年第1期36卷 103-112页

作者：曹傲能上海大学纳米化学与生物学研究所上海200444

蛋白质折叠问题被称为第二遗传密码,至今未破译;蛋白质序列的天书仍然是"句读之不知,惑之不解"。在最近工作的基础上,我们提出了蛋白质结构的"限域下最低能量结构片段"假说。这一假说指出,蛋白质中存在一些关键的长程强相互作用位点,这... 详细信息

蛋白质折叠问题被称为第二遗传密码,至今未破译;蛋白质序列的天书仍然是"句读之不知,惑之不解"。在最近工作的基础上,我们提出了蛋白质结构的"限域下最低能量结构片段"假说。这一假说指出,蛋白质中存在一些关键的长程强相互作用位点,这些位点相当于标点符号,将蛋白质序列的天书变成可读的句子(多肽片段)。这些片段的天然结构是在这些强长程相互作用位点限域下的能量最低状态。完整的蛋白质结构由这些"限域下最低能量结构片段"拼合而成,而蛋白质整体结构并不一定是全局性的能量最低状态。在蛋白质折叠过程中,局部片段的天然结构倾向性为强长程相互作用的形成提供主要基于焓效应的驱动力,而天然强长程相互作用的形成为局部片段的天然结构提供主要基于熵效应的稳定性。在蛋白质进化早期,可能存在一个"石器时代",即依附不同界面(比如岩石)的限域作用而稳定的多肽片段先进化出来,后由这些片段逐步进化(包括拼合)而成蛋白质。

关键词：蛋白质折叠多肽生命起源前杂合体人工蛋白质金抗体

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主动靶向载药脂质体在肿瘤治疗中的研究进展

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生物医学工程学杂志 2022年第3期39卷 633-638页

作者：张曼玉楼晨曦(综述) 曹傲能(审校) 上海大学纳米化学与生物学研究所上海200444

脂质体是理想的药物载体,具有生物相容性好、无免疫原性、表面易功能化等众多优点,并已在肿瘤等疾病的临床治疗中得到应用。对于肿瘤治疗来说,脂质体本身虽然具有一定的被动靶向能力,但单一的被动靶向对提高药物在肿瘤组织的富集率的作... 详细信息

脂质体是理想的药物载体,具有生物相容性好、无免疫原性、表面易功能化等众多优点,并已在肿瘤等疾病的临床治疗中得到应用。对于肿瘤治疗来说,脂质体本身虽然具有一定的被动靶向能力,但单一的被动靶向对提高药物在肿瘤组织的富集率的作用非常有限,主动靶向是提高药物富集率的有效措施。因此几十年来,主动靶向脂质体药物载体获得广泛研究。本文综述了基于载体与肿瘤细胞表面特异性结合的主动靶向脂质体药物载体的研究进展,并总结了该领域存在的机遇、挑战和未来前景。

关键词：脂质体主动靶向肿瘤治疗

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