具有生物活性的多价糖肽的研究进展

糖蛋白复合物是许多疾病诊断与治疗中的重要生物标志分子.糖与蛋白之间的作用通常表现出高度特异性和弱的亲和力,化学家们通过合成多价簇状糖来解决糖亲和力太低的问题.本文对近年来代表性的多价糖肽合成工作及其生物应用做了简要概述.     

天冬甜素的化学合成法研究

甜味剂天冬甜素的合成方法主要有化学合成和酸法合成两大类.本文对化学合成法中五种具有代表性的合成方法进行了实验探讨,并对以不同原料进行缩合反应中间体及最终产物的产率作了研究比较。     

天冬甜素的化学合成法研究

甜味剂天冬甜素的合成方法主要有化学合成和酸法合成两大类．本文对化学合成法中五种具有代表性的合成方法进行了实验探讨，并对以不同原料进行缩合反应中间体及最终产物的产率作了研究比较。     

头孢氨苄酶法合成影响因素概述

头孢氨苄作为第一代口服的头孢菌素类抗生素,对多种革兰阳性菌和革兰阴性菌均有很强的抗菌活性。目前我国制药工业中生产头孢氨苄主要是化学合成法,合成过程步骤繁琐,对环境污染严重。与传统化学合成法相比,生物酶法合成头孢氨苄具有反应条件温和、工艺简便、绿色环保、洁净安全等优点。本文概述了酶法合成头孢氨苄固定化酶的制备,合成过程中各个反应物浓度、温度、pH、投酶量、非水介质对反应转化率的影响以及酶法合成头孢氨苄存在的问题。     

L-半胱氨酸的生产方法及应用进展

L-半胱氨酸是一种具有生理功能的氨基酸,是组成蛋白质的20多种氨基酸中唯一具有还原性基团巯基(-SH)的氨基酸。目前已在医药、食品添加剂和化妆品中广泛应用。L-半胱氨酸的合成主要有毛发水解后还原法、酶法合成法、化学合成法和发酵法以及通过构建基因工程菌来生产等,其中微生物方法生产L-半胱氨酸较化学方法具有相当的优越性,生产步骤简化,底物转化率高,可降低污染,因此微生物酶法生产L-半胱氨酸具有重要的研究意义。     

支链氨基酸代谢在糖肽类和环脂肽类抗生素产量提高与组分优化中的应用

摘要：糖肽类和环脂肽类抗生素具有很好的抗菌活性,临床上广泛用于治疗多重耐药菌导致的严重感染。大部分糖肽类和 环脂肽类抗生素均含有带支链结构的脂肪酸侧链,侧链结构差异是导致这两类抗生素发酵组分多样性的主要原因。支链脂肪酸 侧链的合成起始于支链氨基酸分解代谢,调控支链氨基酸代谢对于定向合成含有特定脂肪酸侧链的糖肽类和环脂肽类抗生素具 有重要作用。本文从糖肽类和环脂肽类抗生素中脂肪酸侧链的生源途径、外源添加支链氨基酸对糖肽类和环脂肽类抗生素产量 和组分的影响,内部改造支链氨基酸代谢途径对糖肽类和环脂肪肽类抗生素产量和组分的影响3方面进行了综述。     

苔藓植物是生物活性物质的一个资源吗？（续）

5 苔藓成分的合成5.1 概述为在大规模生产中得到天然产物并独立地阐明其化学结构,化学合成是个非常重要的手段。尽管迄今已分离到很多苔藓组分并已进行了结构分类,但对这些天然产物的合成相对的知之甚少。已经研究的一些代表性的例子是     

血脑屏障中P-糖蛋白的调节机制

P-糖蛋白属于ABC转运蛋白超家族。它在脑微血管中大量表达,限制毒性物质和大量治疗中枢神经系统的药物进入脑内,因此弄清P-糖蛋白在血脑屏障中的调节机制对疾病的治疗尤为重要。该文总结了P-糖蛋白基本结构、分布、功能,并讨论了P-糖蛋白在血脑屏障中调节机制的研究进展。     

维生素K2的相关合成研究及前景展望

维生素K2属于甲萘醌化合物，对人体心血管、骨质、动脉等组织起到重要防护功能，作为一种新型的保健类食品，已经受到全世界的广泛关注并成为研究热点。目前，维生素K2主要依靠化学合成法和生物发酵法进行生产。本文主要对生产维生素K2的化学合成法和生物发酵法及其相关研究成果，以及对未来市场前景的展望进行综述。     

血小板糖蛋白Ⅵ及其拮抗药物研究进展

胶原和血小板相互作用机制为进一步阐明血栓形成提供了依据；胶原与血小板糖蛋白受体（GPR）及其拮抗药的研究，为预防和早期治疗血栓性疾病开辟新领域。血小板糖蛋白Ⅵ（GPⅥ）是与胶原密切连接的血小板受体。本文综述了血小板糖蛋白Ⅵ的结构、生理功能及其与胶原的相互作用，并介绍其拮抗药研究的一些新进展。     

Conformation-activity relationship of designed glycopeptides as synthetic probes for the detection of autoantibodies, biomarkers of multiple sclerosis

Sera from patients suffering from autoimmune disorders often contain multiple types of autoantibodies, some of which can be exclusive of a disease and thus used as biomarkers for diagnosis. Identification of these autoantibodies, as disease biomarkers, should be achieved using native antigens in simple biological assays. However, posttranslational modifications, such as glycosylation, may play a fundamental role for specific autoantibody recognition. In line with these observations, we described synthetic glycopeptides able to detect high autoantibody titers in sera of patients affected by multiple sclerosis, an inflammatory, demyelinating disease of the central nervous system. We describe here the conformation-activity relationship of a focused library of glycopeptides based on structural diversity, with the aim of defining the structural requirements for the interaction of these glycopeptide antigens with specific autoantibodies. The final goal is the optimization of an antigenic probe for multiple sclerosis, to be used in the development of a simple diagnostic test based on an immunoenzymatic assay. The reported results clearly indicate that glycopeptides able to reveal high antibody titers in multiple sclerosis sera are characterized by a type I' beta-turn around the minimal epitope Asn(Glc), which allows an efficient exposure of this moiety to antibodies interactions, in the context of a solid-phase immunoenzymatic assay.     

Synthesis of diverse asparagine linked oligosaccharides and synthesis of sialylglycopeptide on solid phase

Oligosaccharides are linked to the protein surface and play roles in a number of biological events. Therefore, much attention is being paid to research to investigate the function of the oligosaccharides. In order to investigate the function of oligosaccharides, many synthetic approaches have been examined by synthesizing O-linked or N-linked glycopeptides. Synthesis of O-linked type oligosaccharides is relatively feasible compared to that of N-linked oligosaccharides, because the number of sugar components in the former oligosaccharides is small. In the biosynthesis of oligosaccharides, only N-linked oligosaccharide is reconstructed from the high mannose-type to the hybrid and complex types at the Golgi apparatus. This scientific question, namely, why only N-glycan should change its structure, has been paid much attention and convenient synthesis for both N-glycan and glycopeptide having N-glycans has been examined in order to study the role of N-glycan. In this review, we would introduce recent synthetic developments focusing on the synthesis of N-linked glycopeptides and its analogues.     

Recent developments in reversing glycopeptide-resistant pathogens

Recent studies addressing vancomycin-resistance phenomena are surveyed. Besides leading semi-synthetic glycopeptides: BI-397 and LY 333328, other new synthetic derivatives are also presented. Rational design based on the known mode of action is seen in recent research from both industrial and academic groups. Thus, Biosearch Italia SpA worked on new synthetic glycopeptides with a modified binding pocket in order to find drugs active against both vancomycin-sensitive and -resistant strains. Eli Lilly & Co. and research groups at Stanford, Cambridge and Harvard synthesised covalently linked dimers in order to copy the dimerisation and membrane anchoring effects. Both directions proved to be rewarding and some interesting compounds with potent in vitro activity against vancomycin-resistant enterococci (VRE) were found from these investigations. A new mechanistic proposal that can account for the bioactivity of LY 333328 against VRE was summarised. Research on new agents with modes of action different to that of glycopeptide antibiotics have also been successful and recent investigations related to RP-59500, SCH-27899 and U-100766 are presented.     

Novel antitumor agents: marine sponge alkaloids, their synthetic analogs and derivatives

Present review describes research on novel natural antitumor agents isolated from marine sponges. More than 90 novel cytotoxic antitumor compounds and their synthetic analogs have shown confirmed activity in vitro tumor cell lines bioassay and are of current interest to NCI for further in vivo evaluation. A great problem, to use directly the reservoir of marine organisms for therapy is the very low availability and the isolation of only very small amounts of the biologically active substances from the natural materials. Thus, the synthetic chemistry is required to develop high yield synthetic methods, which are able to produce sufficient marine alkaloids for a broad biological screening. This review will present some of the aspects of the medicinal chemistry developed recently to introduce such modifications. The structures, origins, synthesis and biological activity of a selection of N-heterocyclic marine sponge alkaloids are reviewed. The emphasis is on compounds poised as potential anticancer drugs: pyrroles, pyrazines, imidazole, and other structural families. With computer program PASS some additional biological activities are also predicted, which point toward new possible applications of these compounds. This review emphasizes the role of marine sponge alkaloids as an important source of leads for drug discovery.     

Thio sugars: biological relevance as potential new therapeutics

The biological relevance of sulfur containing carbohydrates is gaining substantial attention. Thus the new developments, especially in the synthetic and medicinal chemistry of thio-sugars are critically important for carbohydrate drug design. New studies of biological processes including biosynthetic reactions and enzyme control mechanisms, discovered during the last few years clearly contributed to an understanding of their biological roles. These roles of carbohydrates and thio-sugars in particular through biological processes and diseases are becoming better understood now. These new trends will provide tremendous opportunities for the development of carbohydrates as new potential drugs. The main objective of this article is to address these new promising advances     

Chemistry and biology of new marine alkaloids from the indole and annelated indole series

Chemistry and biology of marine natural products from the indole and annelated indole series have become an attractive research field for development of new pharmacological lead substances. In the past years some of the isolated natural organic compounds were synthesized by chemists and evaluated with great enthusiasm to find new lead natural compounds against different diseases. In this review the latest results for new compounds including isolation, biological evaluation, synthetic pathways and some retrosynthetic analyses are summarized.     

Synthetic glycopeptides from the mucin family as potential tools in cancer immunotherapy

Compared to glycoproteins of healthy cells, glycoproteins of tumor cells are often aberrantly glycosylated. Thus, glycopeptide fragments of surface glycoproteins of tumor cells are of interest as tumor-associated antigens for the distinction between normal and tumor cells. Cancer immunotherapy directed at selectively targeting these tumor-associated glycoprotein structure alterations--deficient glycosylation and, thus, exposure of peptide epitopes which are masked in normal cells--is considered a promising approach for the treatment of cancer. For this purpose, glycoproteins from the mucin family are of particular interest. Mucins belong to a class of heavily O-glycosylated, high-molecular weight glycoproteins present on the surface of many epithelial cells. The mucin core protein consists of numerous tandem repeats rich in serine, threonine and proline. In their tumor-associated forms, epithelial mucins carry cryptic saccharide structures such as T(N)-, T-, sialyl-T(N)- and sialyl-T antigens and more complex oligosaccharides (e.g. Lewis(y)). In contrast to glycoproteins isolated from natural sources, synthetic glycopeptides can be obtained in high purity and with exactly defined structure. In this review, methodologies for the synthesis of mucin-type glycopeptides containing complex tumor-associated antigen structures are described. Due to the low immunogenicity often exhibited by synthetic tumor-associated glycopeptide antigens, their conjugation to carrier proteins or suitable T-cell epitopes is essential for the development of anti-tumor vaccines. The results of immunological evaluations of synthetic (glyco)peptides and oligosaccharides are described. Some of these synthetic vaccines show promising activities inducing proliferation of T-cells and cytotoxic T-cell responses.     

Synthesis of xanthones: an overview

Among the known synthetic routes to obtain xanthones, the Grover, Shah, and Shah reaction, the cyclodehydration of 2, 2'-dihydroxybenzophenones and electrophilic cycloacylation of 2-aryloxybenzoic acids are the most popular methods. Due to important biological applications of xanthones, some synthetic strategies leading to more complex derivatives have been widely explored in the past years. Thus, the purpose of this review is to report some recent improvements of the classical synthetic methods as well as of some non-classical methods to obtain simple oxygenated xanthones. The strategies for introduction of substituents into the xanthonic nucleus are also summarized. Furthermore, different approaches used to synthesize complex structures, with an emphasis on the total synthesis of bioactive natural products, accomplished in the last twenty years, are also discussed. Besides the synthesis of xanthones, the reactivity of the xanthonic nucleus and its role as a key intermediate for the synthesis of other important classes of compounds are also highlighted.     

The effect of pyridazine compounds on the cardiovascular system

Many natural as well as synthetic heterocylic compounds are known to have different biological activities. The pyridazine moiety is an important structural feature of many biologically active compounds and show diverse pharmacological properties. Pyridazines hold considerable interest relative to the preparation of organic intermediates and physiologically active compounds. However, some compounds bearing pyridazinone rings have been reported to be effective in different cardiovascular diseases. On the basis of the reported literature, we study here on pyridazine compounds to their different biological activities on cardiovascular system. Pyridazinones further draw our focused attention because of their easy fictionalization at various ring positions, which makes them attractive synthetic compounds for designing and development of novel pyridazinone as cardiotonic agents in future.     

Oxazolidinones: a review

The oxazolidinones represent a novel chemical class of synthetic antimicrobial agents. They exhibit an unique mechanism of protein synthesis inhibition and generally display bacteriostatic activity against many important human pathogens, including methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, and penicillin- and cephalosporin-resistant Streptococcus pneumoniae. Linezolid, the oxazolidinone which has been selected for clinical development, has near complete oral bioavailability plus favourable pharmacokinetic and toxicity profiles. Results from experimental models of infection and phase II trials reveal linezolid to be highly active in vivo against infections due to many common gram-positive pathogens. The role of linezolid remains to be determined in phase III clinical trials, but it shows great promise as an alternative to glycopeptides and streptogramins to treat serious infections due to resistant gram-positive organisms. Further modification of the oxazolidinone nucleus may yield agents with even greater potency and with novel spectra of activity.