检索结果-南通市图书馆

Site-directed cysteine coupling of disulfide-containing non-antibody carrier proteins(THIoCAPs)

Science China Materials 2023年第10期66卷 4109-4120页

作者： Ariana Rueda Julian I.Mendoza Lorena Alba-Castellon Eloi Parladé Eric Voltà-Durán David Paez Anna Avino Ramon Eritja Esther Vázquez an.on.o villaverde Ramón Mangues Ugutz Unzueta Institut d'Investigació Biomèdica Sant Pau(IIB Sant Pau) Sant Quintí 77-7908041 BarcelonaSpain Josep Carreras Leukaemia Research Institute(IJC Campus Sant Pau) 08041 BarcelonaSpain CIBER de Bioingeniería Biomateriales y NanomedicinaInstituto de Salud Carlos Ⅲ28029 MadridSpain Institut de Biotecnologia i de Biomedicina Universitat Autònoma de Barcelona08193 BellaterraSpain Departament de Genètica i de Microbiologia Universitat Autònoma de Barcelona08193 BellaterraSpain Department of Medical oncology Hospital de la Santa Creu i Sant Pau.Barcelona08025 BarcelonaSpain CIBER de Enfermedades Raras(CIBERER) Instituto de Salud Carlos Ⅲ28029 MadridSpain Institute for Advanced Chemistry of Catalonia(IQAC) CSIC08034 BarcelonaSpain

The development of a new generation of nonantibody protein drug delivery systems requires site-directed conjugation strategies to produce homogeneous,reproducible and scalable *** that,the genetic addition of cysteine residues into solvent-exposed positions allows the thiol-mediated cysteine coupling of therapeutic drugs into protein-based ***,the high reactivity of unpaired cysteine residues usually reduces protein stability,consequently imposing the use of more methodologically demanding purification *** is especially relevant for disulfide-containing nanocarriers,as previously observed in ***,although many protein scaffolds and targeting ligands are also rich in disulfide bridges,the use of these methodologies over emerging non-antibody carrier proteins has been completely ***,we report the development of a simple and straightforward procedure for a onestep production and site-directed cysteine conjugation of disulfide-containing non-antibody thiolated carrier proteins(THIoCAPs).This method is validated in a fluorescent C-X-C chemokine receptor 4(CXCR4)-targeted multivalent nanocarrier containing two intramolecular disulfide bridges and one reactive cysteine residue strategically placed into a solvent-exposed position(THIo-T22-GFP-H6)for drug conjugation and in a humanized alternative intended for clinical applications(T22-HSNBT-H6).Thus,we produce very stable,homogeneous and fully functional antitumoral nanoconjugates(THIo-T22-GFP-H6-MMAE and T22-HSNBT-H6-MMAE)that selectively eliminate target cancer cells via ***,the developed methodology appears as a powerful tool for the rational engineering of emerging non-antibody,cell-targeted protein nanocarriers that contain disulfide bridges together with a solvent-exposed reactive cysteine(THIoCAP).This should pave the way for the development of a new generation of stable,homogeneous and efficient nanomedicines.

关键词： disulfide directed bridges

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

The spectrum of building block conformers sustains the biophysical properties of clinically-oriented self-assembling protein nanoparticles

引用

Science China Materials 2022年第6期65卷 1662-1670页

作者： Eric Voltà-Durán Julieta M Sánchez Hèctor-López-Laguna Eloi Parladé Laura Sánchez-García Alejandro Sánchez-Chardi Ario de Marco Ugutz Unzueta Esther Vázquez an.on.o villaverde Institut de Biotecnologia i de Biomedicina Universitat Autònoma de BarcelonaBellaterra 08193BarcelonaSpain Departament de Genètica i de Microbiologia Universitat Autònoma de BarcelonaBellaterra 08193BarcelonaSpain CIBER de Bioingeniería Biomateriales y Nanomedicina(CIBER-BBN) Bellaterra 08193BarcelonaSpain Instituto de Investigaciones Biológicas y Tecnológicas(IIBYT)(CoNICET-Universidad Nacional de Córdoba) ICTA&Cátedra de Química BiológicaDepartamento de QuímicaFCEFyNUNC.Av.Velez Sarsfield 1611X 5016GCA CórdobaArgentina Servei de Microscòpia Universitat Autònoma de BarcelonaBellaterra 08193BarcelonaSpain Departament de Biologia Evolutiva Ecologia i Ciències AmbientalsFacultat de BiologiaUniversitat de Barcelona08028 BarcelonaSpain Laboratory for Environmental and Life Sciences University of Nova GoricaNova Gorica 5000Slovenia Biomedical Research Institute Sant Pau(IIB Sant Pau) Sant Antoni Ma Claret 16708025 BarcelonaSpain

Histidine-rich peptides confer self-assembling properties to recombinant proteins through the supramolecular coordination with divalent *** fact allows the cost-effective,large-scale generation of microscopic and macroscopic protein materials with intriguing biomedical *** such materials,resulting from the simple bioproduction of protein building blocks,homomeric nanoparticles are of special value as multivalent interactors and drug ***,we have here identified that the assembly of a given His-tagged protein might render distinguishable categories of self-assembling protein *** fact has been scrutinized through the nanobody-containing fusion proteins EM1-GFP-H6 and A3C8-GFP-H6,whose biosynthesis results in two distinguishable populations of building *** one of them,the assembling and disassembling is controllable by ***,a second population immediately self-assembles upon purification through a non-regulatable pathway,rendering larger nanoparticles with specific biological *** structural analyses of both model proteins and nanoparticles revealed important conformational variability in the building *** fact renders different structural and functional categories of the final soft materials resulting from the participation of energetically unstable intermediates in the oligomerization *** data illustrate the complexity of the Hismediated protein assembling in recombinant proteins but they also offer clues for a better design and refinement of protein-based nanomedicines,which,resulting from biological fabrication,show an architectonic flexibility unusual among biomaterials.

关键词： recombinant proteins self-assembling protein materials nanoparticles biomaterials

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

Endosomal escape of protein nanoparticles engineered through humanized histidine-rich peptides

引用

Science China Materials 2020年第4期63卷 644-653页

作者： Hector Lopez-Laguna Rafael Cubarsi Ugutz Unzueta Ramon Mangues Esther Vazquez an.on.o villaverde Institut de Biotecnologia i de Biomedicina Universitat Aut6noma de BarcelonaBellaterra08193 BarcelonaSpain Departament de Genetica i de Microbiologia Universitat Aut6noma de BarcelonaBellaterra08193 BarcelonaSpain CIBER de Bioingenieria Biomateriales y Nanomedicina(CIBER-BBN)C/Monforte de Lemos 3-528029 MadridSpain Departament de Matematiques Universitat Politecnica de Catalunya08034BarcelonaSpain Institut d'Investigacions Biomediques Sant Pau Hospital de la Santa Creu i Sant Pau08025 BarcelonaSpain

Poly-histidine peptides such as H6(HHHHHH)are used in protein biotechnologies as purification tags,protein-assembling agents and endosomal-escape *** pleiotropic properties of such peptides make them appealing to design protein-based smart materials or nanoparticles for imaging or drug delivery to be produced in form of recombinant ***,the clinical applicability of H6-tagged proteins is restricted by the potential immunogenicity of these *** this study,we have explored several humanized histidine-rich peptides in tumor-targeted modular proteins,which can specifically bind and be internalized by the target cells through the tumoral marker *** were particularly interested in exploring how protein purification,self-assembling and endosomal escape perform in proteins containing the variant histidine-rich *** the tested candidates,the peptide H5 E(HEHEHEHEH)is promising as a good promoter of endosomal escape of the associated fulllength protein upon endosomal *** numerical modelling of cell penetration and endosomal escape of the tested proteins has revealed a negative relationship between the amount of protein internalized into target cells and the efficiency of cytoplasmic *** fact demonstrates that the His-mediated,proton sponge-based endosomal escape saturates at moderate amounts of internalized protein,a fact that might be critical for the design of protein materials for cytosolic molecular delivery.

关键词： protein materials nanoparticles genetic design endosomal escape poly-histidines

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

Self-assembling protein nanocarrier for selective delivery of cytotoxic polypeptides to CXCR4^(+) head and neck squamous cell carcinoma tumors

引用

Acta Pharmaceutica Sinica B 2022年第5期12卷 2578-2591页

作者： Elisa Rioja-Blanco Irene Arroyo-Solera Patriciaálamo Isolda Casanova Alberto Gallardo Ugutz Unzueta Naroa Serna Laura Sánchez-García Miquel Quer an.on.o villaverde Esther Vázquez Ramon Mangues Lorena Alba-Castellón Xavier León Institut d'InvestigacióBiomèdica Sant Pau(IIB-Sant Pau) Barcelona 08041Spain Institut de Recerca contra la Leucèmia Josep Carreras Barcelona 08025Spain CIBER de Bioingeniería Biomateriales y Nanomedicina(CIBER-BBN)Madrid 28029Spain Department of Pathology Hospital de la Santa Creu i Sant PauBarcelona 08041Spain Institut de Biotecnologia i de Biomedicina Universitat Autònoma de BarcelonaBellaterra 08193Spain Departament de Genètica i de Microbiologia Universitat Autònoma de BarcelonaBellaterra 08193Spain Department of otorhinolaryngology Hospital de la Santa Creu i Sant PauBarcelona 08041Spain

Loco-regional recurrences and distant metastases represent the main cause of head and neck squamous cell carcinoma(HNSCC) mortality. The overexpression of chemokine receptor 4(CXCR4) in HNSCC primary tumors associates with higher risk of developing loco-regional recurrences and distant metastases, thus making CXCR4 an ideal entry pathway for targeted drug delivery. In this context, our group has generated the self-assembling protein nanocarrier T22-GFP-H6, displaying multiple T22 peptidic ligands that specifically target CXCR4. This study aimed to validate T22-GFP-H6 as a suitable nanocarrier to selectively deliver cytotoxic agents to CXCR4^(+)tumors in a HNSCC model. Here we demonstrate that T22-GFP-H6 selectively internalizes in CXCR4^(+)HNSCC cells, achieving a high accumulation in CXCR4^(+)tumors in vivo, while showing negligible nanocarrier distribution in non-tumor bearing organs. Moreover, this T22-empowered nanocarrier can incorporate bacterial toxin domains to generate therapeutic nanotoxins that induce cell death in CXCR4-overexpressing tumors in the absence of histological alterations in normal organs. Altogether, these results show the potential use of this T22-empowered nanocarrier platform to incorporate polypeptidic domains of choice to selectively eliminate CXCR4^(+)cells in HNSCC. Remarkably, to our knowledge, this is the first study testing targeted proteinonly nanoparticles in this cancer type, which may represent a novel treatment approach for HNSCC patients.

关键词： Targeted drug delivery Protein nanoparticles CXCR4 receptor HNSCC Cell targeting Recombinant proteins Nanotoxins Cancer therapy

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

Provincial Disparities in Post-reform China

引用

China & World Economy 2010年第2期18卷 73-95页

作者： José villaverde Adolfo Maza Bala Ramasamy University of Cantabria China Europe International Business School

Using conventional and novel techniques, the present paper analyzes the main characteristics of Chinese provincial disparities during the reform period, specifically between 1978 and 200Z After dismissing the presence of spatial dependence, three main results are obtained： first, provincial inequalities have basically followed a ＂V＂ trend; second, grouping China into three large regions shows that inequality mainly lies within each region, particularly in coastal areas; and third, the analysis of intra-distribution dynamics reveals that, although there was some significant mobility in provincial relative income, particularly until 1990, the whole periodpersistence in the ranking of income levels is a major feature. This might provoke some changes in the policy approach to dealing with spatial disparities.

关键词： China convergence growth intra-distribution dynamics provincial disparities

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

Controlling self-assembling and tumor cell-targeting of protein-only nanoparticles through modular protein engineering

引用

Science China Materials 2020年第1期63卷 147-156页

作者： Eric Volta-Duran olivia Cano-Garrido Naroa Serna Hector Lopez-Laguna Laura Sanchez-Garcia Mireia Pesarrodona Alejandro Sanchez-Chardi Ramon Mangues an.on.o villaverde Esther Vazquez Ugutz Unzueta Institut de Biotecnologia i de Biomedicina Universitat Autònoma de BarcelonaBellaterra08193 BarcelonaSpain Departament de Genetica i de Microbiologia Universitat Autònoma de BarcelonaBellaterra08193 BarcelonaSpain CIBER de Bioingeniería Biomateriales y Nanomedicina(CIBER-BBN)C/Monforte de Lemos 3-528029 MadridSpain Nanoligent SL Edifici EUREKAUniversitat Autonoma de BarcelonaBellaterra08193 BarcelonaSpain Institut dInvestigacions Biomèdiques Sant Pau and Josep Carreras Research Institute Hospital de la Santa Creu i Sant Pau08041 BarcelonaSpain Departament de Biologia Evolutiva Ecologia i Ciencies AmbientalsFacultat de BiologiaUniversitat de BarcelonaAv.Diagonal 64308028 BarcelonaSpain Institute for Research in Biomedicine(IRB Barcelona) The Barcelona Institute of Science and Technology08028 BarcelonaSpain

Modular protein engineering is suited to recruit complex and multiple functionalities in single-chain polypeptides. Although still unexplored in a systematic way, it is anticipated that the positioning of functional domains would impact and refine these activities, including the ability to organize as supramolecular entities and to generate multifunctional protein materials. To explore this concept, we have repositioned functional segments in the modular protein T22-GFP-H6 and characterized the resulting alternative fusions. In T22-GFP-H6, the combination of T22 and H6 promotes selfassembling as regular nanoparticles and selective binding and internalization of this material in CXCR4-overexpressing tumor cells, making them appealing as vehicles for selective drug delivery. The results show that the pleiotropic activities are dramatically affected in module-swapped constructs, proving the need of a carboxy terminal positioning of H6 for protein self-assembling, and the accommodation of T22 at the amino terminus as a requisite for CXCR4^+ cell binding and internalization. Furthermore, the failure of self-assembling as regular oligomers reduces cellular penetrability of the fusions while keeping the specificity of the T22-CXCR4 *** these data instruct how multifunctional nanoscale protein carriers can be designed for smart, protein-driven drug delivery, not only for the treatment of CXCR4^+ human neoplasias, but also for the development of anti-HIV drugs and other pathologies in which CXCR4 is a relevant homing marker.

关键词： nanoparticles protein materials recombinant proteins drug delivery self-assembling cancer cell targeting

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

Behaviour of Structural Carbon Steel at High Temperatures

引用

材料科学与工程（中英文A版） 2012年第7期2卷 501-510页

作者： Juan an.on.o Trilleros villaverde Irene Huertas Gonzalez Department of Materials Science and Metallurgical Engineering Universitas Complutensis of Madrid Ciudad Universitaria s/nMadrid 28040 Spain

The research develops an experimental study on two carbon steels used for construction of structures on civil works, S355NL and S460NL, to high temperatures with values ranging between 500 °C and 950 °C. In order to obtain experimental evidence of behavior of steels at elevated temperatures, the chemical and structural characterizations and tested steels were made, deducing the found microstructures and average grain sizes measured. Tensile tests at elevated temperatures were made and steels mechanical properties were deducted at different temperatures. Also hardness steels tests were made. Creep and plastic deformation phenomena were observed from micrography and fractography studies.

关键词：建筑结构碳素钢高温行为实验证据拉伸试验土建工程研究开发

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

Recent advances in bird sperm morphometric analysis and its role in male gamete characterization and reproduction technologies

引用

Asian Journal of Andrology 2016年第6期18卷 882-888页

作者： Julian Santiago-Moreno Milagros Cristina Esteso Silvia villaverde-Morcillo Adolfo Toledano-Diaz Cristina Castafio Rosario Velazquez an.on.o Lopez-Sebastian Agustin Lopez Goya Javier Gimeno Martinez Department of Animal Reproduction INIA 28040 Madrid Spain Veterinary Clinical and Research Services Fieb Foundation 28760 Tres Cantos Madrid Spain FAUNIA 28032 Madrid Spain

Postcopulatory sexual selection through sperm competition may be an important evolutionary force affecting many reproductive traits, including sperm morphometrics. Environmental factors such as pollutants, pesticides, and climate change may affect different sperm traits, and thus reproduction, in sensitive bird species. Many sperm-handling processes used in assisted reproductive techniques may also affect the size of sperm cells. The accurately measured dimensions of sperm cell structures （especially the head） can thus be used as indicators of environmental influences, in improving our understanding of reproductive and evolutionary strategies, and for optimizing assisted reproductive techniques （e.g., sperm cryopreservation） for use with birds. Computer-assisted sperm morphometry analysis （CASA-Morph） provides an accurate and reliable method for assessing sperm morphometry, reducing the problem of subjectivity associated with human visual assessment. Computerized systems have been standardized for use with semen from different mammalian species. Avian spermatozoa, however, are filiform, limiting their analysis with such systems, which were developed to examine the approximately spherical heads of mammalian sperm cells. To help overcome this, the standardization of staining techniques to be used in compute^-assessed light microscopical methods is a priority. The present review discusses these points and describes the sperm morphometric characteristics of several wild and domestic bird species.

关键词： avian computer-assisted assay morphometry spermatozoa

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

Temperature Field on Structural Carbon Steel under Fire Conditions

引用

材料科学与工程（中英文B版） 2011年第6期1卷 725-735页

作者： Juan an.on.o Trilleros villaverde Sonia Mato Diaz Irene Huertas Gonzalez Department of Materials Science and Metallurgical Engineering Universitas Complutensis of Madrid Ciudad Universitaria s/nMadrid 28040 Spain

The behaviour of structural steels components subjected to a high temperature field depends not only on the absolute temperature reached, but also on the temperature versus time function and heating rate. The research objective of the present work was the determination of the heating rate impact on selected strength parameters of structural steels. Tests were carried out on structural carbon steel in order to find experimental parameters required for the limit state analysis of steel structures under the thermal conditions as occur in fires. An electrical furnace has been designed and constructed to simulate the effect of the fire in buildings, which allowed treat a sample thermally following the temperature profile for the different standard curves of fire. For this purpose, an electrical controller has been used to heat the furnace and to control the experimental temperatures achieves into the furnace when a specific fire curve was applied. The furnace temperature time fields for the internal and external faces of the sample as well as the furnace atmosphere were registered. A spreadsheet method was used to predict the temperature of the steel samples and compare them with temperatures obtained experimentally, following the European Convention for Constructional Steelwork.

关键词：碳素结构钢温度场电气控制器火焰实验参数曲线轮廓绝对温度加热速率

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

重组氯毒素构建细胞靶向的活性纳米颗粒(英文)

引用

Science China Materials 2019年第6期62卷 892-898页

作者： Raquel Díaz Laura Sánchez-García Naroa Serna Alejandro Sánchez-Chardi olivia Cano-Garrido Julieta M.Sánchez Ugutz Unzueta Esther Vazquez an.on.o villaverde Institut de Biotecnologia i de Biomedicina Universitat Autònoma de Barcelona Departament de Genètica i de Microbiologia Universitat Autònoma de Barcelona CIBER de Bioingeniería Biomateriales y Nanomedicina(CIBER-BBN) Servei de Microscòpia Universitat Autònoma de Barcelona Biomedical Research Institute Sant Pau(IIB-Sant Pau)and Josep Carreras Research Institute Hospital de la Santa Creu i Sant Pau Universidad Nacional de Córdoba Facultad de Ciencias ExactasFísicas y Naturales.ICTA and Departamento de QuímicaCátedra de Química Biológica.Córdoba.Argentina.CONICETInstituto de Investigaciones Biológicas y Tecnológicas(IIBYT)

功能性蛋白质在纳米尺度的可控寡聚化提供了通过重组DNA技术来设计和生产改良材料和药物的可能性.氯毒素(CTX),作为一种重组的蝎毒素,由于其优先结合癌细胞的能力而引起人们的兴趣.本研究将氯毒素设计并自组装为12 nm的常规纳米颗粒,这... 详细信息

功能性蛋白质在纳米尺度的可控寡聚化提供了通过重组DNA技术来设计和生产改良材料和药物的可能性.氯毒素(CTX),作为一种重组的蝎毒素,由于其优先结合癌细胞的能力而引起人们的兴趣.本研究将氯毒素设计并自组装为12 nm的常规纳米颗粒,这些纳米颗粒可穿透具有和天然毒素相同受体特异性的培养细胞.这些生物相容且可生物降解的材料,表现出与同时作为载体和治疗剂的重组毒素相应的温和但仍然显著的细胞毒活性,有希望成为用于细胞靶向治疗胶质瘤的药物载体.此外,对CTX侧区域的修改可有效影响纳米颗粒的性能,说明基于CTX的构建体可通过常规基因工程来调节其多重功能性.

关键词：重组DNA技术细胞毒活性纳米颗粒蝎毒素癌细胞可生物降解氯药物载体

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：