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。     

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 Pseudomonas aeruginosa,CRPA)耐药机制及高危因素的角度出发,为临床控制和治疗耐碳青霉烯类铜绿假单胞菌提供帮助。     

Cover Feature: Exploring the Flexibility of the Glycopeptide Antibiotic Crosslinking Cascade for Extended Peptide Backbones (ChemBioChem 6/2023)

The glycopeptide antibiotics (GPAs) are a clinically approved class of antimicrobial agents that classically function through the inhibition of bacterial cell-wall biosynthesis by sequestration of the precursor lipid II. The oxidative crosslinking of the core peptide by cytochrome P450 (Oxy) enzymes during GPA biosynthesis is both essential to their function and the source of their synthetic challenge. Thus, understanding the activity and selectivity of these Oxy enzymes is of key importance for the future engineering of this important compound class. Recent reports of GPAs that display an alternative mode of action and a wider range of core peptide structures compared to classic lipid II-binding GPAs raises the question of the tolerance of Oxy enzymes for larger changes in their peptide substrates. In this work, we explore the ability of Oxy enzymes from the biosynthesis pathways of lipid II-binding GPAs to accept altered peptide substrates based on a vancomycin template. Our results show that Oxy enzymes are more tolerant of changes at the N terminus of their substrates, whilst C-terminal extension of the peptide substrates is deleterious to the activity of all Oxy enzymes. Thus, future studies should prioritise the study of Oxy enzymes from atypical GPA biosynthesis pathways bearing C-terminal peptide extension to increase the substrate scope of these important cyclisation enzymes.     

Understanding the Glycopeptide Antibiotic Crosslinking Cascade: In Vitro Approaches Reveal the Details of a Complex Biosynthesis Pathway

The glycopeptide antibiotics (GPAs) are a fascinating example of complex natural product biosynthesis, with the nonribosomal synthesis of the peptide core coupled to a cytochrome P450-mediated cyclisation cascade that crosslinks aromatic side chains within this peptide. Given that the challenges associated with the synthesis of GPAs stems from their highly crosslinked structure, there is great interest in understanding how biosynthesis accomplishes this challenging set of transformations. In this regard, the use of in vitro experiments has delivered important insights into this process, including the identification of the unique role of the X-domain as a platform for P450 recruitment. In this minireview, we present an analysis of the results of in vitro studies into the GPA cyclisation cascade that have demonstrated both the tolerances and limitations of this process for modified substrates, and in turn developed rules for the future reengineering of this important antibiotic class.     

Photocatalytic Degradation of Some Typical Antibiotics: Recent Advances and Future Outlooks

The existence of antibiotics in the environment can trigger a number of issues by fostering the widespread development of antimicrobial resistance. Currently, the most popular techniques for removing antibiotic pollutants from water include physical adsorption, flocculation, and chemical oxidation, however, these processes usually leave a significant quantity of chemical reagents and polymer electrolytes in the water, which can lead to difficulty post-treating unmanageable deposits. Furthermore, though cost-effectiveness, efficiency, reaction conditions, and nontoxicity during the degradation of antibiotics are hurdles to overcome, a variety of photocatalysts can be used to degrade pollutant residuals, allowing for a number of potential solutions to these issues. Thus, the urgent need for effective and rapid processes for photocatalytic degradation leads to an increased interest in finding more sustainable catalysts for antibiotic degradation. In this review, we provide an overview of the removal of pharmaceutical antibiotics through photocatalysis, and detail recent progress using different nanostructure-based photocatalysts. We also review the possible sources of antibiotic pollutants released through the ecological chain and the consequences and damages caused by antibiotics in wastewater on the environment and human health. The fundamental dynamic processes of nanomaterials and the degradation mechanisms of antibiotics are then discussed, and recent studies regarding different photocatalytic materials for the degradation of some typical and commonly used antibiotics are comprehensively summarized. Finally, major challenges and future opportunities for the photocatalytic degradation of commonly used antibiotics are highlighted.     

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.     

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。     

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。     

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。     

An Original and Efficient Antibiotic Adjuvant Strategy to Enhance the Activity of Macrolide Antibiotics against Gram-Negative Resistant Strains

Gram-negative bacteria were reported as a significant cause of infections in both community and nosocomial settings. Considered as one of the greatest threats to public health, the spread of bacteria drug resistance and the lack of effective alternative treatment options remains problematic. Herein, we report a promising strategy to combat Gram-negative resistant strains consisting of the combination of a macrolide antibiotic with a polyaminoisoprenyl adjuvant derivative leading to a significant decrease of antibiotic resistance.