新型糖肽类抗生素雷莫拉宁研究进展

雷莫拉宁为7个组份组成的抗生素混合物,因其攻击细菌的方式让细菌不易产生抵抗性,因此产生抗药菌株的可能性较低,其在用于治疗革兰氏阳性菌引起的感梁性疾病中有良好前景。     

糖肽类抗生素雷莫拉宁的研究

雷莫拉宁(Ramoplanin、A 16686、MDL 62,198)是一种新型的糖肽类抗生素,能够特异而迅速地抑制革兰氏阳性菌细胞壁的生物合成,其抑菌机制与万古霉素(Vancomycin)和替考拉宁(Teicoplanin)不同,但是其对葡萄球菌的抑菌率是万古霉素和替考拉宁的4～8倍,对许多具有耐药性的病原菌也有很好的抑菌效果.同时雷莫拉宁的细胞毒性较小且无交叉耐药问题.雷莫拉宁的纯品是由A 1、A 2、A 3 3个组分组成的混合物,其中A 2为主要成分,占80%.     

新型糖肽类抗生素达巴万星

达巴万星是一种新型注射用半合成糖肽抗生素,适用于复杂感染及多重耐药菌造成感染的抗菌治疗。其对革兰阳性病原体有抗菌活性,且对耐甲氧西林金黄色葡萄球菌(MRSA)具有特别强力的活性;对耐G+病原菌包括耐青霉素和头孢曲松肺炎链球菌、替考拉宁不敏感CoNS、非vanA型肠球菌具有活性;对G+厌氧菌也具有活性。介绍了达巴万星的特性、制备工艺以及临床试验,指出了达巴万星具有独特的药动学性质,通过微生物发酵获得,在治疗导管相关的血源性感染以及皮肤和软组织感染已取得了良好的效果,是理想的第二代糖肽抗生素。     

糖肽类抗生素奥利万星及其中间体生物的研究

抗生素药物管理的缺失,造成耐药菌数量逐渐增多,抗生素用药需求也逐渐增多.奥利万星作为糖肽类抗生素药物,主要用于治疗革兰氏阳性菌感染.本文结合已有研究,分析了奥利万星的作用机制,总结了奥利万星及其中间体生物的研究进展.     

抗菌新药替考拉宁市场前景看好

替考拉宁在与氨基糖苷类药物合用时，比万古霉素等其它糖肽类抗生素对肾功能的影响要小得多，且很少引起糖肽类抗生素所致的过敏反应。     

雷莫拉宁的分离纯化工艺研究

以聚酰胺树脂为分离介质,研究了从发酵液中分离纯化雷莫拉宁的工艺过程,对吸附及解吸条件进行了优化。结果表明,在雷莫拉宁浸提液浓度为1600～2000μg.mL-1、吸附流速为1.0BV.h-1、乙醇作洗脱剂(先用30%或50%乙醇洗脱,再用70%乙醇洗脱)的条件下,可得到总收率超过80%、纯度大于95%的雷莫拉宁,该方法简单易行、安全性高,适于工业化生产。     

耐碳青霉烯类铜绿假单胞菌耐药机制及高危因素的研究进展

碳青霉烯是一种非典型内酰胺类药物,因为它抗菌谱广,抗菌能力强等特征,临床上常用于医治重大的细菌感染.近期,随着此类药物的普遍运用,致使一些肠杆菌科细菌(如铜绿假单胞菌)对其敏感性逐年下降.此类现象的出现,导致临床对这类细菌的医治相当棘手.本文将从耐碳青霉烯类铜绿假单胞菌(Carbapenem resistant Pse...     

Synthesis and Immunological Evaluation of a Multicomponent Cancer Vaccine Candidate Containing a Long MUC1 Glycopeptide

A fully synthetic MUC1‐based cancer vaccine was designed and chemically synthesized containing an endogenous helper T‐epitope (MHC class II epitope). The vaccine elicited robust IgG titers that could neutralize cancer cells by antibody‐dependent cell‐mediated cytotoxicity (ADCC). It also activated cytotoxic T‐lymphocytes. Collectively, the immunological data demonstrate engagement of helper T‐cells in immune activation. A synthetic methodology was developed for a penta‐glycosylated MUC1 glycopeptide, and antisera of mice immunized by the new vaccine recognized such a structure. Previously reported fully synthetic MUC1‐based cancer vaccines that elicited potent immune responses employed exogenous helper T‐epitopes derived from microbes. It is the expectation that the use of the newly identified endogenous helper T‐epitope will be more attractive, because it will activate cognate CD4⁺ T‐cells that will provide critical tumor‐specific help intratumorally during the effector stage of tumor rejection and will aid in the generation of sustained immunological memory.     

Enantiomeric Separation of Fused Polycycles by HPLC with Cyclodextrin and Macrocyclic Glycopeptide Chiral Stationary Phases

Abstract

The enantiomeric separation of a series of 13 new chiral polycycles has been examined on both cyclodextrin‐based and macrocyclic glycopeptide chiral stationary phases (CSPs) using HPLC in the normal phase, reversed phase, and polar organic modes. The most effective chiral selectors for the enantiomeric separation of these analytes are the 2,3‐dimethyl‐β‐cyclodextrin (Cyclobond I‐2000 DM) and hydroxypropyl‐β‐cyclodextrin (Cyclobond I‐2000 RSP). The other Cyclobond‐type and Chirobiotic (macrocyclic glycopeptide) CSPs only show enantioselectivity for a few of the racemic polycycles. The effects of mobile phase composition and analyte structure on chiral recognition and separation are considered.     

农用抗生素作用机理简述

归纳了我国近20年来大规模使用的多种农用抗生素作用机理的主要类型,并对作用机理的研究方法与应用进行了讨论。     

碳青霉烯类抗生素的研究进展

碳青霉烯类抗生素具有很好临床应用价值和市场前景,本文将从碳青霉烯类抗生素的研发史、上市品种、以及面临的问题等方面讨论、阐述该类抗生素的研究概况及发展前景。     

头孢菌素类抗生素的中国专利战略分析

头孢菌素类药物是目前临床广泛应用的抗生素。本文以头孢菌素类抗生素药物的中国专利数据为分析样本,从品种分布、申请人状况、地区分布以及国内外申请人的专利布局等角度人手,对国内外申请人的头孢菌素类药物专利领域的战略进行分析,为国内的医药企业制定专利战略提供参考。     

Isolation and Structure Characterization of an Antioxidative Glycopeptide from Mycelial Culture Broth of a Medicinal Fungus

A novel glycopeptide (Cs-GP1) with an average molecular weight (Mw) of 6.0 kDa was isolated and purified by column chromatography from the lower Mw fraction of exopolysaccharide (EPS) produced by a medicinal fungus Cordyceps sinensis Cs-HK1. Its carbohydrate moiety was mainly composed of glucose and mannose at 3.2:1.0 mole ratio, indicating an O-linked glycopeptide. The peptide chain contained relatively high mole ratios of aspartic acid, glutamic acid and glycine (3.3–3.5 relative to arginine) but relatively low ratios of tyrosine and histidine. The peptide chain sequence analyzed after trypsin digestion by LC-MS was KNGIFQFGEDCAAGSISHELGGFREFREFLKQAGLE. Cs-GP1 exhibited remarkable antioxidant capacity with a Trolox equivalent antioxidant capacity of 1183.8 μmol/g and a ferric reducing ability of 611.1 μmol Fe(II)/g, and significant protective effect against H₂O₂-induced PC12 cell injury at a minimum dose of 10 μg/mL. This is the first report on the structure and bioactivity of an extracellular glycopeptide from the Cordyceps species.     

紫外可见分光光度法在抗生素类药物分析中的应用

综述了近年来紫外可见分光光度法在抗生素药物分析中的应用,其中包括β-内酰胺类、氨基糖苷类、四环素类、大环内酯类、喹诺酮类抗生素;并展望了该方法今后的发展趋势.     

Harnessing the Synthetic Capabilities of Glycopeptide Antibiotic Tailoring Enzymes: Characterization of the UK‐68,597 Biosynthetic Cluster

In this study, a draft genome sequence of Actinoplanes sp. ATCC 53533 was assembled, and an 81‐kb biosynthetic cluster for the unusual sulfated glycopeptide UK‐68,597 was identified. Glycopeptide antibiotics are important in the treatment of infections caused by Gram‐positive bacteria. Glycopeptides contain heptapeptide backbones that are modified by many tailoring enzymes, including glycosyltransferases, sulfotransferases, methyltransferases, and halogenases, generating extensive chemical and functional diversity. Several tailoring enzymes in the cluster were examined in vitro for their ability to modify glycopeptides, resulting in the synthesis of novel molecules. Tailoring enzymes were also expressed in the producer of the glycopeptide aglycone A47934, generating additional chemical diversity. This work characterizes the biosynthetic program of UK‐68,597 and demonstrates the capacity to expand glycopeptide chemical diversity by harnessing the unique chemistry of tailoring enzymes.     

动物源性食品中抗生素残留检测技术研究进展

抗生素在禽畜业生产中的不合理使用现象非常普遍,其所造成的食品安全问题也较为严峻。抗生素残留检测是控制食品安全质量的重要环节,当前的抗生素残留检测方法主要是利用生物、化学工程中的一些分离与鉴别手段,实现对样品中目标组分的分离与鉴定。文章对当前抗生素检测的研究现状进行了梳理,分析了各种检测技术的优缺点,并对食品工业化抗生素检测技术的研究方向提出了建议。