综述人工合成型抗菌肽及其药学应用研究进展

天然抗菌肽（antimicrobial peptides, AMPs）是一类小分子阳离子多肽,具备多种杀菌机制,呈现出高效、广谱的杀菌特性,在抑制耐药性细菌、制备新型抗菌素等方面具有重要的研究价值。以天然抗菌肽为蓝本,设计和开发的人工合成型抗菌肽可以有效克服天然抗菌肽对蛋白酶敏感、细胞毒性较大、生产成本高等缺陷,作为抗感染的潜在药物具有更广阔的应用前景。综述了目前主要的抗菌肽人工改造技术,包括化学修饰法、蛋白质工程技术、计算机分子模拟技术和从头设计最小化抗菌肽方法的研究进展,并对人工合成抗菌肽作为抗菌药物的应用现状进行了简介。     

抗菌肽融合表达研究进展

抗菌肽抗菌谱广、活性稳定,且具有与抗生素不同的抗菌机制,在抑杀病原微生物的同时不易产生耐药性,因而在食品、饲料、医药等领域具有重要的应用价值。基因工程技术是降低抗菌肽生产成本的主要方式,其中融合表达在提高抗菌肽产量方面起到了重要作用。文中综述了抗菌肽融合表达的国内外研究进展,探讨了部分融合标签用于抗菌肽表达的策略,并对今后的发展提出了自己的看法。     

昆虫抗菌肽分类及在医学中应用

昆虫是地球上种类最为繁多的生物,其抗菌肽的种类和应用范围也远多于其他生物产生的抗菌肽。随着越来越多昆虫抗菌肽的发现及对其深入的研究,昆虫抗菌肽的结构和作用机制也被逐一阐明,并广泛应用于畜牧、食品工业及医药等领域。然而,由于某些限制因素,昆虫抗菌肽还未应用于临床。为了加快昆虫抗菌肽在临床中的应用,本文将从昆虫抗菌肽的结构分类、潜在的医学应用以及昆虫抗菌肽的生产研究现状等方面作一综述,以期为昆虫抗菌肽在抗细菌、抗病毒、抗肿瘤及抗寄生虫药物等方面的医用研发提供文献支持。     

两栖类动物Cathelicidins家族 抗菌肽研究进展

两栖类动物皮肤裸露和湿润的特性易于微生物的生长,它们为了抵御病原微生物的侵袭,在长期自然进化过程中形成了以抗菌肽(AMPs)为主要防御机制的免疫系统。抗菌肽广泛分布于动物、植物、微生物中,是生物用于抵御细菌、真菌、病毒和原虫等病原体侵袭的重要武器之一,在进化上是一类非常古老而有效的天然防御物质。Cathelicidins是脊椎动物特有的重要抗菌肽家族之一,除具有高效广谱的抗菌活性,还具有如抗炎、抗氧化、伤口修复、抑制组织损伤和促进血管生成等多种重要活性,因此Cathelicidins家族抗菌肽已成为抗感染多肽类新药的研发热点。本文将从两栖类动物Cathelicidins家族抗菌肽的一般特点、来源分布、生物合成与结构、生物学活性、作用机制及应用前景等几个方面,综合阐述国内外的研究动态。     

我国研制出新型基因工程抗菌肽

国家海洋局第三海洋研究所日前采用先进分子生物学技术,克隆鱼类抗菌肽基因,生产出LYC基因工程抗菌肽,并建立基因工程抗菌肽的中试生产工艺和生产线。研究人员将以此为基础研制开发无公害环保型水产抗菌新药。     

含有Fxa切割位点的抗菌肽X在大肠杆菌中的融合表达

抗菌肽是昆虫体液免疫的重要成分[1,2 ] ,它们的分子量较小 ,具有抗菌、抗病毒和杀伤某些肿瘤细胞的功能 ,而不破坏人体正常细胞。基于它的这种选择性效应和分子小、无抗原性的特点 ,可望成为新一代的抗菌、抗肿瘤药物。然而 ,天然抗菌肽来源十分困难 ,不能满足研究和临床应用的需要 ,通过基因工程技术生产抗菌肽已成为人们普遍关注的焦点。抗菌肽ＣＭＩＶ是从家蚕蛹中分离并测定了其一级结构的新型抗菌肽 ,它由 35个氨基酸组成 ,不含甲硫氨酸 ,Ｃ 末端为酰胺[3 ] 。抗菌肽Ｘ是中国家蚕抗菌肽ＣＭＩＶ的变体 ,其一级结构与天然的抗菌肽ＣＭ…     

抗菌肽研究进展

抗菌肽是广泛存在于自然界生物中的一种具有抗菌、抗病毒和抗肿瘤活性的多态,由于抗菌肽具有普通抗生素所不具有的一系列优点,抗菌肽的研究已经成了现代学术和应用研究的一个热点。作者综述了抗菌肽的抗菌机制和应用研究等方面的内容。     

基因工程制药的研究现状与发展前景

简要叙述了近年来基因工程技术在医药工业中的应用进展,主要包括基因工程技术在药物生产、新药开发及药物生产工艺改进的应用.随着基因组和蛋白质组研究的深入,基因工程药物将有更多的机会获得突破性进展.     

生物信息学用于抗菌肽预测和分子设计的研究进展

抗菌肽(AMP)以其特异性抗菌、抗病毒、抗肿瘤功能及快速、广谱、高效等特点,迅速成为具有重要研究价值的新型生物活性肽。寻找合适方法最大限度提高其活性,降低毒性和成本,是新型抗菌肽药物研发过程中面临的首要问题。应用生物信息学工具对新型抗菌肽进行预测或对天然抗菌肽进行分子设计成为解决这一问题的关键。对生物信息学在抗菌肽预测和优化设计中的最新进展进行综述,以期扩大抗菌肽的来源,提高现有抗菌肽的生物活性。     

抗菌肽magainin Ⅱ的密码子优化及在大肠杆菌和毕赤酵母中的表达

Magainin Ⅱ是非洲爪蟾皮肤分泌的一种抗菌肽,在低浓度下即能够对细菌、真菌、原虫、肿瘤等都具有杀伤作用,并且与同是来源于非洲爪蟾皮肤的另一种抗菌肽PGLa在杀菌、抗肿瘤等方面具有很好的协同效应。文中分别按照大肠杆菌和毕赤酵母的密码子利用频率,对抗菌肽magainin Ⅱ以及杂合抗菌肽magainin Ⅱ-PGLa,进行了密码子优化。构建了高效表达抗菌肽magainin Ⅱ的原核表达载体,经过蛋白酶切割获得纯化的抗菌肽magainin Ⅱ。同时进一步构建了杂合抗菌肽magainin Ⅱ-PGLa的分泌型毕赤酵母表达载体,实现了杂合抗菌肽在毕赤酵母中的分泌表达。本研究为magainin Ⅱ和magainin Ⅱ-PGLa的生产与应用奠定了基础。     

N-terminal amphipathic helix as a trigger of hemolytic activity in antimicrobial peptides: A case study in latarcins

In silico structural analyses of sets of α-helical antimicrobial peptides (AMPs) are performed. Differences between hemolytic and non-hemolytic AMPs are revealed in organization of their N-terminal region. A parameter related to hydrophobicity of the N-terminal part is proposed as a measure of the peptide propensity to exhibit hemolytic and other unwanted cytotoxic activities. Based on the information acquired, a rational approach for selective removal of these properties in AMPs is suggested. A proof of concept is gained through engineering specific mutations that resulted in elimination of the hemolytic activity of AMPs (latarcins) while leaving the beneficial antimicrobial effect intact.     

Applications of antimicrobial peptides from fish and perspectives for the future

Fish are a major component of the aquatic fauna. Like other organisms, fish secrete different kinds of antimicrobial peptides (AMPs), which are positively charged short amino-acid-chain molecules involved in host defense mechanisms. Environmental hazards and the greenhouse effect have led to increased evolution of drug- and vaccine-resistant pathogenic strains, and it is necessary to find new drugs with structural uniqueness to fight them. Aquatic sources contain thousands of fish species, and each secretes AMPs with structural differences which can be used by the pharmaceutical industry in its search for novel drugs to treat drug-resistant pathogens. Not only limited to antimicrobial functions, AMPs possess other desirable characteristics which may be exploited in the near future. In this review, we list fish AMPs available from published reports, and discuss application-oriented functions of these AMPs. Notably, the possibilities of using fish AMPs as antimicrobial agents, vaccine adjuvants, inactivated vaccines, and antitumor agents are discussed in this review.     

Collection of antimicrobial peptides database and its derivatives: Applications and beyond

Collection of antimicrobial peptides (CAMP), CAMPSign, and ClassAMP are open‐access resources that have been developed to enhance research on antimicrobial peptides (AMPs). Comprehensive information on AMPs and machine learning‐based predictive models are made available for users through these resources. As of date, CAMP_R3 has 10,247 sequences, 757 structures, and 114 family‐specific signatures of AMPs along with associated tools for AMP sequence and structure analysis. CAMPSign uses family‐specific sequence conservation, in the form of patterns and hidden Markov models for identification of AMPs. ClassAMP can be used to classify AMPs as antibacterial, antifungal, or antiviral based on sequence information. Here we describe CAMP and its derivatives and illustrate, with a few examples, the contribution of these online resources to the advancement of our current understanding of AMPs.     

Molecular cloning and functional characterization of novel antimicrobial peptides from the skin of brown frog, Rana zhenhaiensis

Rana zhenhaiensis, a species of brown frog, is widely distributed in central and south China. In the present study, a total of 14 cDNA sequences encoding eight novel antimicrobial peptides (AMPs) were cloned from the synthesized cDNAs of R. zhenhaiensis skin. The eight novel AMPs belong to four families: brevinin-1 (four peptides), brevinin-2 (one peptide), ranatuerin-2 (one peptide) and chensinin-1 (two peptides), five AMPs from the four families (brevinin-1ZHa, brevinin-1ZHb, brevinin-2ZHa, ranatuerin-2ZHa and chensinin-1ZHa) were chemically synthesized, their antimicrobial and hemolytic activities were examined. The results indicated that the five AMPs possess different antimicrobial and hemolytic activities. Of these, brevinin-2ZHa exhibited the strongest and most broad-spectrum antimicrobial activity. Furthermore, scanning electron microscopy (SEM) experiment was carried out to investigate the potential antimicrobial mechanism of chensinin-1ZHa. The result indicated that chensinin-1ZHa may exert its function through disruption of the bacterial membrane.     

改良型抗菌肽的研究进展

长期滥用抗生素导致了耐药菌株“超级细菌”的出现,增加了动物、人类健康和环境污染风险．寻找抗生素替代品正成为全球研究热点,抗菌肽因其高效抗菌效果和不同于抗生素的独特作用机制引起了各国研究者的关注,并进行了相关研究．然而抗菌肽的安全性、稳定性、生产成本等问题限制了其生产与应用．为了克服这些不利因素,研究者们对抗菌肽进行了多种方式的改造,产生了模拟型、同源型、杂合型、轭合型、稳定型和固位型等改良型抗菌肽,并有望在畜牧业、食品业、医药业等领域得到广泛的应用．本文主要综述了这些改良型抗菌肽近年来的研究进展．     

Defense peptides of plant immune system

Antimicrobial peptides (AMPs) are natural antibiotics produced by all living organisms to combat pathogens. They are important effector molecules of the immune system both in animals and plants. AMPs are diverse in structure and mode of action. Based on homology of amino acid sequences and 3D structures several AMP families have been distinguished. They are defensins, thionins, lipid transfer proteins, hevein- and knottin-like peptides, and cyclotides. AMPs display broad-spectrum antimicrobial activity and thus show promise for the development of disease- resistant crops by genetic engineering and for the production of new-generation drugs. In this paper, the properties of the main AMP families (defensins and hevein-like peptides) and of a new 4-Cys plant AMP family are reviewed.     

Defense peptides of plant immunity

Antimicrobial peptides (AMPs) are natural antibiotics produced by all living organisms to fight pathogens. They are important effector molecules of the immune system both in animals and plants. AMPs are diverse in structure and mode of action. Based on the homology of amino acid sequences and 3D structures several AMP families have been distinguished. They are defensins, thionins, lipid transfer proteins, hevein- and knottin-like peptides, and cyclotides. AMPs display broad-spectrum antimicrobial activity and thus show promise for the development of disease-resistant crops by genetic engineering and for the production of new-generation drugs. In this paper, the properties of the main AMP families (defensins and hevein-like peptides) and of new 4-Cys plant AMP family are reviewed.