量子点在癌症研究中的应用

半导体量子点具有长时间、多目标和灵敏度高等独特的光化学性质,这些特性使量子点成为细胞标记和生物应用中得到了广泛的应用。利用量子点目标定位癌细胞,对于寻找癌变部位具有指导的作用。近年来,利用量子点作为光动力学治疗癌症的能量供体也得到了一定的研究。简单地介绍了量子点独特的光学性质,并从量子点标记癌细胞、可视化癌细胞表面功能和在光动力学治疗癌症等方面综述了量子点在癌症诊断和治疗中的应用。     

量子点在生物学中的应用

量子点是一种无机荧光材料,它具有独特的光物理特性,如其激发光谱宽且连续分布,而发射光谱呈对称分布且宽度窄,而且可通过改变量子点内核的尺寸对其发射光波长进行精细调节等。量子点的这些特性正引起人们日益广泛的关注,并在很多领域得到了应用。本文介绍了量子点的组成以及它的光学特性,同时介绍并讨论了近年来量子点在生物学领域应用的进展以及存在的问题。     

量子点在生命科学中的应用

近年来 ,量子点 (半导体纳米微晶体 )的研究引起国内外研究者的广泛兴趣 ,其研究内容涉及物理、化学、材料等多学科 ,已成为一门新兴的交叉学科。虽然量子点在生物学中的应用才刚刚起步 ,但是已经取得了有意义的进展 ,成为人们极为注意的一个热点。现就量子点的光学特性、制备方法以及在生物学中的研究进展和应用前景作一简要综述     

高通量药物筛选技术进展及新药开发策略

新药研发过程中．通过筛选而获得具有生物活性的先导化合物．是创新药物研究的关键．目前药物筛选模型已经从传统的整体动物、器官和组织水平发展到细胞和分子水平。创新药物的发现都离不开采用适当的药物作用靶点对大量化合物样品进行筛选．而且筛选规模越大,发现新药的机会就越多。随着计算机技术、生物芯片、蛋白质组学、组合化学等的发展．高通量药物筛选技术应运而生。高通量筛选体系在创新药物筛选中的应用是新药开发研究的一个重要领域。     

量子点在生物医学中的应用

半导体量子点是无机纳米结晶,构成于硒化镉核心和硫化锌外壳.这种荧光标记物的发射光强是常用有机荧光染料的20倍,稳定性是其100倍.量子点的发射波长取决于核心粒子的大小,而每一种单色量子点的发射波长窄而对称.这些光学特性使量子点在医学诊断、药物的高速筛选以及基因和蛋白质的高通量分析方面具有广泛的应用前景.基于量子点的稳定性和生物相容性,有可能通过标记不同颜色的量子点到不同的分子,观察它们在活细胞内的运动.     

量子点在基因转染中的应用研究进展

量子点因其独特的纳米尺寸效应、光学特性和生物相容性,既能作为纳米载体与目的基因结合,又能作为纳米荧光标记物跟踪记录其在转染过程中的位置,给基因工程的发展带来了新的契机。在阐述量子点用于基因转染的优势、标记基因的方法等基础上,作者系统综述了量子点在基因转染中的应用,并对其发展趋势和应用前景进行了展望。     

量子点荧光探针在生物成像中的应用进展

量子点荧光探针是近几年发展起来的一种新型荧光标记物,拥有荧光染料及荧光蛋白所不能比拟的独特优势,已经在细胞功能研究及细胞表面和内部功能分子的探测、组织的成像和病灶的定位等方面得到了较为广泛的应用。本文对量子点的光学特性、生物化修饰及其在生物成像等方面的应用进展进行了较为详细的介绍,并展望了其应用发展。     

功能化量子点在肿瘤诊治中的应用

量子点是一种半导体纳米晶体,它可发出激发荧光,具有亮度高、稳定时间长和发射光谱可调节等特性,是同时检测多信号的良好材料.这些独特性质使得它们在肿瘤诊治领域中的应用日益受到人们的重视.对量子点进行功能化修饰,如偶联抗体等活性物质后,可以对肿瘤细胞进行特异性识别及示踪,以实现对肿瘤的诊断和治疗.文中分别从分子靶向识别、淋巴结定位和药物传递等方面探讨了功能化量子点在肿瘤诊断和治疗中的最新进展.此外,还讨论了量子点的毒性以及用于肿瘤检测和治疗的多功能量子点的设计方法,并提出了其实际应用的潜在方向.     

量子点的生命科学中的应用

近年来,最子点（半导体纳米微晶体）的研究引起国内外研究者的广泛兴趣,其研究内容涉及物理、化学、材料等多材料,已成为一门新兴的交叉学科。虽然量子点在生物学中的应用才刚刚起步,但是已经取得了意义的进展,成为人们极为注意的一个热点。现就量子点的光学特性、制备方法以及在生物学中的研究进展和应用前景作一简要综述。     

量子点在生物学中的研究进展

量子点作为一种新型的荧光标记物近年来已在生物学中获得广泛应用。本文总结了量子点的主要光学特性,其中包括荧光激发和发射光谱特性、量子产额、光漂白特性和荧光寿命等。重点综述了量子点在细胞标记、活体和组织成像、组合标记和光动力学治疗等生物学中的应用及其最新研究进展。同时讨论了量子点在应用中可能存在的细胞毒性等主要问题,最后对量子点在生物学中的应用前景作了展望。     

A solid-phase glycosyltransferase assay for high-throughput screening in drug discovery research

Glycosyltransferases mediate changes in glycosylation patterns which, in turn, may affect the function of glycoproteins and/or glycolipids and, further downstream, processes of development, differentiation, transformation and cell-cell recognition. Such enzymes, therefore, represent valid targets for drug discovery. We have developed a solid-phase glycosyltransferase assay for use in a robotic high-throughput format. Carbohydrate acceptors coupled covalently to polyacrylamide are coated onto 96-well plastic plates. The glycosyltransferase reaction is performed with recombinant enzymes and radiolabeled sugar-nucleotide donor at 37°C, followed by washing, addition of scintillation counting fluid, and measurement of radioactivity using a 96-well -counter. Glycopolymer construction and coating of the plastic plates, enzyme and substrate concentrations, and linearity with time were optimized using recombinant Core 2 1-6-N-acetylglucosaminyltransferase (Core 2 GlcNAc-T). This enzyme catalyzes a rate-limiting reaction for expression of polylactosamine and the selectin ligand sialyl-Lewis^x in -glycans. A glycopolymer acceptor for 1-6-N-acetylglucosaminyltransferase V was also designed and shown to be effective in the solid-phase assay. In a high-throughput screen of a microbial extract library, the coefficient of variance for positive controls was 9.4%, and high concordance for hit validation was observed between the Core 2 GlcNAc-T solid-phase assay and a standard solution-phase assay. The solid-phase assay format, which can be adapted for a variety of glycosyltransferase enzymes, allowed a 5–6 fold increase in throughput compared to the corresponding solution-phase assay.     

Yeast and drug discovery

Advanced genetic techniques, along with the high degree of conservation of basic cellular processes, have made the yeast Saccharomyces cerevisiae a valuable system for identification of new drug targets, target-based and non-target-based drug screening, and detailed analysis of the cellular effects of drugs. Yeast also presents a convenient system for antifungal drug discovery because it is closely related to Candida albicans, a major human pathogen. Many yeast genes remain poorly characterized, and most of the sophisticated techniques in yeast have been in widespread use less than a decade – a period shorter than the typical cycle from target identification to marketing approval for a new drug. It is likely that most of the benefits of yeast in discovery and development of therapeutic compounds have yet to be realized. Electronic Publication     

斑马鱼在新药发现中的应用

在过去20年里,斑马鱼已成为一种重要的模式脊椎动物,在发育、遗传、免疫、肿瘤和毒理等诸多研究领域中被广泛应用。近年来,斑马鱼作为活体模型越来越多地应用于某些生物学过程的药物筛选。通过斑马鱼初步筛选,在药物研发初期可确定化合物的生物学活性、毒性以及副作用等。最近的研究还发现,斑马鱼不仅用于新药筛选,还可用于药物结构的优化。本文重点介绍斑马鱼在新药发现中的应用。     

Genetics-directed drug discovery for combating Mycobacterium tuberculosis infection

Mycobacterium tuberculosis (Mtb), the pathogen of tuberculosis (TB), is one of the most infectious bacteria in the world. The traditional strategy to combat TB involves targeting the pathogen directly; however, the rapid evolution of drug resistance lessens the efficiency of this anti-TB method. Therefore, in recent years, some researchers have turned to an alternative anti-TB strategy, which hinders Mtb infection through targeting host genes. In this work, using a theoretical genetic analysis, we identified 170 Mtb infection-associated genes from human genetic variations related to Mtb infection. Then, the agents targeting these genes were identified to have high potential as anti-TB drugs. In particular, the agents that can target multiple Mtb infection-associated genes are more druggable than the single-target counterparts. These potential anti-TB agents were further screened by gene expression data derived from connectivity map. As a result, some agents were revealed to have high interest for experimental evaluation. This study not only has important implications for anti-TB drug discovery, but also provides inspirations for streamlining the pipeline of modern drug discovery.     

Potential clinical applications of quantum dots

The use of luminescent colloidal quantum dots in biological investigations has increased dramatically over the past several years due to their unique size-dependent optical properties and recent advances in biofunctionalization. In this review, we describe the methods for generating high-quality nanocrystals and report on current and potential uses of these versatile materials. Numerous examples are provided in several key areas including cell labeling, biosensing, in vivo imaging, bimodal magnetic-luminescent imaging, and diagnostics. We also explore toxicity issues surrounding these materials and speculate about the future uses of quantum dots in a clinical setting.     

Weak affinity chromatography as a new approach for fragment screening in drug discovery

Fragment-based drug design (FBDD) is currently being implemented in drug discovery, creating a demand for developing efficient techniques for fragment screening. Due to the intrinsic weak or transient binding of fragments (mM–μM in dissociation constant (K_D)) to targets, methods must be sensitive enough to accurately detect and quantify an interaction. This study presents weak affinity chromatography (WAC) as an alternative tool for screening of small fragments. The technology was demonstrated by screening of a selected 23-compound fragment collection of documented binders, mostly amidines, using trypsin and thrombin as model target protease proteins. WAC was proven to be a sensitive, robust, and reproducible technique that also provides information about affinity of a fragment in the range of 1 mM–10 μM. Furthermore, it has potential for high throughput as was evidenced by analyzing mixtures in the range of 10 substances by WAC–MS. The accessibility and flexibility of the technology were shown as fragment screening can be performed on standard HPLC equipment. The technology can further be miniaturized and adapted to the requirements of affinity ranges of the fragment library. All these features of WAC make it a potential method in drug discovery for fragment screening.     

"Click"化学在药物发现中的应用

“click”化学是最近几年发展起来的一种新技术,它在药物发现的许多方面均有着广泛的应用:快速合成小分子化合物库并从中筛选先导化合物、进行靶标导向的活性小分子合成以及在生物耦联技术等方面的应用。     

Aqueous synthesis of highly stable CdTe/ZnS Core/Shell quantum dots for bioimaging

In this work, we report the synthesis, characterization and biological application of highly stable CdTe/ZnS (cadmium tellurite/zinc sulphide) Core/Shell (CS) quantum dots (QDs) capped with mercaptosuccinic acid (MSA). The CS QDs were synthesized using a simple one‐pot aqueous method. The synthesized CdTe/ZnS CS QDs were found to exhibit excellent stability even 100 days after preparation and also showed better photoluminescence quantum yield (PLQY) of about 50% compared with that of only CdTe QDs which was nearly 12%. The formation of the CdTe/ZnS CS was confirmed by high‐resolution transmission electron microscopy (HR‐TEM), and Fourier transform infra‐red (FTIR) and X‐ray diffraction (XRD) analyses. Further, on extending our study towards bioimaging of E. coli cells using the QDs samples, we found that CdTe/ZnS CS QDs showed better results compared with CdTe QDs.     

The integration of investigative toxicology in the drug discovery process

Summary— Integrating toxicology early in the drug discovery process adds value by providing the earliest possible identification of a compound's potential for toxicological and pathological effects relevant to intended clinical use. With this approach true ‘lead’ candidates, with a high probability of clinical success, are identified and advanced while reducing effort and resources expended on compounds without the requisite therapeutic index. Resources are focussed on the speed of getting a discovery ‘lead’ into early clinical development, defining the mechanisms of observed preclinical toxicity and their relevance to human use, and developing early safety data with in vitro test systems ahead of in vivo systems where possible, thus reducing animal use.