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多肽、蛋白类药物脂质体的研究进展 总被引:1,自引:0,他引:1
脂质体做为多肽、蛋白类药物一种新型给药载体有控制药物释放、降低药物的毒性、提高药物的靶向性等突出优点,具有广阔的应用前景。本文通过查阅近10年来多肽和蛋白类药物脂质体研究的相关资料,总结论述了脂质体作为多肽、蛋白类药物载体在新的制备方法、新型脂质体、给药途径、产业化进展四个方面的最新研究动向,指出了多肽、蛋白类药物脂质体在研究应用中存在的不足,并展望了多肽、蛋白类药物脂质体未来发展的方向。 相似文献
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A major focus of systems biology is to characterize interactions between cellular components, in order to develop an accurate picture of the intricate networks within biological systems. Over the past decade, protein microarrays have greatly contributed to advances in proteomics and are becoming an important platform for systems biology. Protein microarrays are highly flexible, ranging from large-scale proteome microarrays to smaller customizable microarrays, making the technology amenable for detection of a broad spectrum of biochemical properties of proteins. In this article, we will focus on the numerous studies that have utilized protein microarrays to reconstruct biological networks including protein-DNA interactions, posttranslational protein modifications (PTMs), lectin-glycan recognition, pathogen-host interactions and hierarchical signaling cascades. The diversity in applications allows for integration of interaction data from numerous molecular classes and cellular states, providing insight into the structure of complex biological systems. We will also discuss emerging applications and future directions of protein microarray technology in the global frontier. 相似文献
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糖尿病是一组以高血糖为特征的代谢性疾病,是由于胰岛素分泌缺陷或其生物功能受损,或两者兼有引起。糖尿病可能导致各种组织,特别是眼、肾、心脏、血管、神经的慢性损害、功能障碍。糖尿病主要分为Ⅰ型糖尿病和Ⅱ型糖尿病,这两类糖尿病均存在明显的遗传异质性。目前用于降低或控制血糖的药物主要有硫脉类、双肌类、苯甲酸衍生物类、糖苷酶抑制剂类和噻唑烷二酮类。研发出安全有效的降糖药物已经成为全世界关注的焦点,其中,生物活性肽是目前最广泛研究的潜在治疗剂之一,其最佳用途正在开发中。迄今为止,已经发现了许多天然肽和合成肽,其具有通过不同机制介导的优异的抗糖尿病效果。新兴技术和药物输送系统的应用进一步促进了预期目标成果的达成。临床前和临床研究中一些具有更好效力和安全性的优秀肽已经被确定。因此,对这些肽的进一步详细研究可能会筛选出临床上有用的抗糖尿病药物。 相似文献
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Kaltashov IA Bobst CE Abzalimov RR Wang G Baykal B Wang S 《Biotechnology advances》2012,30(1):210-222
Biopharmaceuticals are a unique class of medicines due to their extreme structural complexity. The structure of these therapeutic proteins is critically important for their efficacy and safety, and the ability to characterize it at various levels (from sequence to conformation) is critical not only at the quality control stage, but also throughout the discovery and design stages. Biological mass spectrometry (MS) offers a variety of approaches to study structure and behavior of complex protein drugs and has already become a default tool for characterizing the covalent structure of protein therapeutics, including sequence and post-translational modifications. Recently, MS-based methods have also begun enjoying a dramatic growth in popularity as a means to provide information on higher order structure and dynamics of biotechnology products. In particular, hydrogen/deuterium exchange MS and charge state distribution analysis of protein ions in electrospray ionization (ESI) MS offer a convenient way to assess the integrity of protein conformation. Native ESI MS also allows the interactions of protein drugs with their therapeutic targets and other physiological partners to be monitored using simple model systems. MS-based methods are also applied to study pharmacokinetics of biopharmaceutical products, where they begin to rival traditional immunoassays. MS already provides valuable support to all stages of development of biopharmaceuticals, from discovery to post-approval monitoring, and its impact on the field of biopharmaceutical analysis will undoubtedly continue to grow. 相似文献
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Towards high-yield production of pharmaceutical proteins with plant cell suspension cultures 总被引:1,自引:0,他引:1
“Molecular farming” in plants with significant advantages in cost and safety is touted as a promising platform for the production of complex pharmaceutical proteins. While whole-plant produced biopharmaceuticals account for a significant portion of the preclinical and clinical pipeline, plant cell suspension culture, which integrates the merits of whole-plant systems with those of microbial fermentation, is emerging as a more compliant alternative “factory”. However, low protein productivity remains a major obstacle that limits extensive commercialization of plant cell bioproduction platform. This review highlights the advantages and recent progress in plant cell culture technology and outlines viable strategies at both the biological and process engineering levels for advancing the economic feasibility of plant cell-based protein production. Approaches to overcome and solve the associated challenges of this culture system that include non-mammalian glycosylation and genetic instability will also be discussed. 相似文献
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Barnett YA Eger K Eriksson S Folkers G Hansen PE Hofbauer R Komitowsky D Milon A Munch-Petersen B;European Thymidine Kinase Study Group 《Biotechnology advances》1994,12(4):663-668
A precondition for the chemotherapeutic treatment of a variety of virally-induced human diseases and malignant conditions is a highly selective interaction of the drug molecule to be used with it's biological target. To ensure the development of novel, effective drugs, it is essential that the biological target is well characterised with regard to it's structure and activity. Such characterisation relies upon adequate amounts of pure target being available. One of the most important enzymatic importers for antimetabolites is the enzyme thymidine kinase. In this article an in vitro protein expression system is described which facilitates the production of milligram amounts of pure and biologically active thymidine kinase, from a number of important biological sources. Results have shown that the in vitro produced enzyme has the exact biochemical propeties of the in vivo enzyme. Thus the in vitro protein expression system is an ideal vechicle to facilitate an in depth investigation of the enzyme's biological properties. 相似文献
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Cell-free protein synthesis systems can synthesize proteins with high speed and accuracy, but produce only a low yield because of their instability over time. Here we review our recent advances in a cell-free protein synthesis system prepared from wheat embryos. We first addressed and resolved the source of the instability of existing systems in light of endogenous ribosome-inactivating proteins. We found that conventional wheat germ extracts contained the RNA N-glycosidase tritin and other inhibitors such as thionin, ribonucleases, deoxyribonucleases, and proteases that originate from the endosperm and inhibit translation. Extensive washing of wheat embryos to eliminate endosperm contaminants has resulted in extracts with a high degree of stability and activity. To maximize the translation yield and throughput of the system, we then focused on developing the following issues: optimization of the ORF flanking regions, a new strategy to construct PCR-generated DNAs for screening, and design of an expression vector for large-scale protein production. The resulting system achieves high-throughput expression, with a PCR-directed system at least 50 genes that can be translated in parallel, yielding between 0.1 and 2.3 mg of protein by one person within 2 days. Under the dialysis mode of reaction, the system with the expression vector can maintain productive translation for 14 days. The cell-free system described here bypasses most of the biological processes and lends itself to robotic automation for high-throughput expression of genetic information, thus opening up many possibilities in the post-genome era. 相似文献
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《Expert review of proteomics》2013,10(4):425-430
Dried blood spots (DBS), a micro blood sampling technique, has recently gained interest in drug discovery and development due to its inherent advantages over the conventional whole blood, plasma or serum sample collection. Since the regulatory authorities have agreed to the use of blood as an acceptable biological matrix for drug exposure measurements, its applications have been extended not only to therapeutic drug monitoring but also to toxicokinetic and pharmacokinetic studies. The pharmaceutical industry is keen to promote DBS as a prominent tool in bioanalytical applications due to the financial, ethical and organizational issues involved in clinical trials. This could be accomplished due to the latest advances in modern analytical technology, particularly liquid chromatography–mass spectrometry. The present review discusses some of the emerging liquid chromatography–mass spectrometry technologies in improving DBS analysis for its innovative applications in the development of new drugs. 相似文献
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Here, we review the use of different biochemical approaches for biological synthesis of circular or backbone-cyclized proteins and peptides. These methods allow the production of circular polypeptides either in vitro or in vivo using standard recombinant DNA expression techniques. Protein circularization can significantly impact protein engineering and research in protein folding. Basic polymer theory predicts that circularization should lead to a net thermodynamic stabilization of a folded protein by reducing the entropy associated with the unfolded state. Protein cyclization also provides a valuable tool for exploring the effects of topology on protein folding kinetics. Furthermore, the biological production of cyclic polypeptides makes possible the production of cyclic polypeptide libraries. The generation of such libraries, which was previously restricted to the domain of synthetic chemists, now offers biologists access to highly diverse and stable molecular libraries for probing protein structure and function. 相似文献
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Yoshikawa T Okada N Oda A Matsuo K Matsuo K Mukai Y Yoshioka Y Akagi T Akashi M Nakagawa S 《Biochemical and biophysical research communications》2008,366(2):408-413
Nanoscopic therapeutic systems that incorporate biomacromolecules, such as protein and peptides, are emerging as the next generation of nanomedicine aimed at improving the therapeutic efficacy of biomacromolecular drugs. In this study, we report that poly(γ-glutamic acid)-based nanoparticles (γ-PGA NPs) are excellent protein delivery carriers for tumor vaccines that delivered antigenic proteins to antigen-presenting cells and elicited potent immune responses. Importantly, γ-PGA NPs efficiently delivered entrapped antigenic proteins through cytosolic translocation from the endosomes, which is a key process of γ-PGA NP-mediated anti-tumor immune responses. Our findings suggest that the γ-PGA NP system is suitable for the intracellular delivery of protein-based drugs as well as tumor vaccines. 相似文献
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《Biotechnology advances》2019,37(8):107455
Living cells are emerging as therapeutic entities for the treatment of patients affected with severe and chronic diseases where no conventional drug can provide a definitive cure. At the same time, the promise of cell-based therapies comes with several biological, regulatory, economic, logistical, safety and engineering challenges that need to be addressed before translating into clinical practice. Among the complex operations required for their manufacturing, cell expansion occupies a significant part of the entire process and largely determines the number, the phenotype and several other critical quality attributes of the final cell therapy products (CTPs). This review aims at characterizing the main culture systems and expansion processes used for CTP production, highlighting the need to implement scalable, cost-efficient technologies together with process optimization strategies to bridge the gap between basic scientific research and commercially available therapies. 相似文献
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Analysis of protein glycosylation by mass spectrometry 总被引:1,自引:0,他引:1
Bo Nilsson 《Molecular biotechnology》1994,2(3):243-280
There is a growing pharmaceutical market for protein-based drugs for use in therapy and diagnosis. The rapid developments
in molecular and cell biology have resulted in production of expression systems for manufacturing of recombinant proteins
and monoclonal antibodies. These proteins are glycosylated when expressed in cell systems with glycosylation ability. For
glycoproteins intended for therapeutic administration it is important to have knowledge about the structure of the carbohydrate
side chains to avoid cell systems that produce structures, which in humans can cause undesired reactions, e.g., immunological
and unfavorable serum clearance rate. Structural analysis of glycoprotein oligosaccharides requires sophisticated instruments
like mass spectrometers and nuclear magnetic resonance spectrometers. However, before the structural analysis can be conducted,
the carbohydrate chains have to be released from the protein and purified to homogeneity, and this is often the most time-consuming
step. Mass spectrometry has played and still plays an important role in analysis of protein glycosylation. The superior sensitivity
compared to other spectroscopic methods is its main asset. Structural analysis of carbohydrates faces several problems, however,
due to the chemical nature of the constituent monosaccharide residues. For oligosaccharides or glycoconjugates, the structural
information from mass spectrometry is essentially limited to monosaccharide sequence, molecular weight, and only in exceptional
cases glycosidic linkage positions can be obtained. In order to completely establish an oligosaccharide structure, several
other structural parameters have to be determined, e.g., linkage positions, anomeric configuration and identification of the
monosaccharide building blocks. One way to address some of these problems is to work on chemical pretreatment of the glycoconjugate,
to specifically modify the carbohydrate chain. In order to introduce specific modifications, we have used periodate oxidation
and trifluoroacetolysis with the objective of determining glycosidic linkage positions by mass spectrometry. 相似文献
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Many therapeutic glycoproteins have been successfully generated in plants. Plants have advantages regarding practical and economic concerns, and safety of protein production over other existing systems. However, plants are not ideal expression systems for the production of biopharmaceutical proteins, due to the fact that they are incapable of the authentic human N-glycosylation process. The majority of therapeutic proteins are glycoproteins which harbor N-glycans, which are often essential for their stability, folding, and biological activity. Thus, several glyco-engineering strategies have emerged for the tailor-making of N-glycosylation in plants, including glycoprotein subcellular targeting, the inhibition of plant specific glycosyltranferases, or the addition of human specific glycosyltransferases. This article focuses on plant N-glycosylation structure, glycosylation variation in plant cell, plant expression system of glycoproteins, and impact of glycosylation on immunological function. Furthermore, plant glyco-engineering techniques currently being developed to overcome the limitations of plant expression systems in the production of therapeutic glycoproteins will be discussed in this review. 相似文献
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Natural products have immense therapeutic potential not only due to their structural variation and complexity but also due
to their range of biological activities. Research based on natural products has led to the discovery of molecules with biomedical
and pharmaceutical applications in different therapeutic areas like cancer, inflammation responses, diabetes, and infectious
diseases. There are still several challenges to be overcome in natural product drug discovery research programs and the challenge
of high throughput screening of natural substances is one of them. Bioactivity screening is an integral part of the drug discovery
process and several in vitro and in vivo biological models are now available for this purpose. Among other well-reported biological
models, the zebrafish (Danio rerio) is emerging as an important in vivo model for preclinical studies of synthetic molecules in different therapeutic areas.
Zebrafish embryos have a short reproductive cycle, show ease of maintenance at high densities in the laboratory and administration
of drugs is a straightforward procedure. The embryos are optically transparent, allowing for the visualization of drug effects
on internal organs during the embryogenesis process. In this review, we illustrate the importance of using zebrafish as an
important biological model in the discovery of bioactive drugs from natural sources. 相似文献
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The targeted delivery of therapeutic peptide by nanocarriers systems requires the knowledge of interactions of nanomaterials with the biological environment, peptide release, and stability of therapeutic peptides. Therapeutic application of nanoencapsulated peptides are increasing exponentially and >1000 peptides in nanoencapsulated form are in different clinical/trial phase. This review covers current scenario of therapeutic protein and peptides encapsulation on polymer to metallic nanocarriers including methods of protein encapsulation, peptide bioconjugation on nanoparticles, stability enhancement of encapsulated proteins and its biomedical applications. 相似文献
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Bo-Rahm Lee Suhyung Cho Yoseb Song Sun Chang Kim Byung-Kwan Cho 《Molecules and cells》2013,35(5):359-370
Synthetic biology is an emerging discipline for designing and synthesizing predictable, measurable, controllable, and transformable biological systems. These newly designed biological systems have great potential for the development of cheaper drugs, green fuels, biodegradable plastics, and targeted cancer therapies over the coming years. Fortunately, our ability to quickly and accurately engineer biological systems that behave predictably has been dramatically expanded by significant advances in DNA-sequencing, DNA-synthesis, and DNA-editing technologies. Here, we review emerging technologies and methodologies in the field of building designed biological systems, and we discuss their future perspectives. 相似文献