专肽生物_定制多肽合成服务_多肽合成定制服务_多肽合成厂家_多肽合成公司

Bactenecin是一种从牛嗜中性粒细胞中分离出的环状阳离子抗菌肽，序列中一共含有12氨基酸。由第三位半胱氨酸C3和第十一位半胱氨酸C11之间巯基氧化形成二硫键环。由于二硫键的存在使得它的结构更趋于稳定。

Bactenecin, a cyclic cationic dodecapeptide, was isolated from bovine neutrophil granules. Bactenecin exhibits a remarkable antibacterial activity in vitro which is comparable to that of the defensins.

Bactenecin (Bactenecin, bovine) 是一种从牛嗜中性粒细胞中分离出来的有效的含 12 个氨基酸的环状抗菌肽，氨基酸序列为RLCRIVVIRVCR。Bactenecin 抑制细菌和酵母菌 (bacteria和yeast) 的生长，并能杀死真菌红毛癣菌 (fungusTrichophyton rubrum)。Bactenecin 增加了膜的通透性，抑制了假苹果芽孢杆菌 (B. pseudomallei) 的生长和生物膜的形成。

Bactenecin的抗菌活性
1、广泛的抗菌谱

Bactenecin具有广泛的抗菌活性，包括针对某些分枝杆菌，这些分枝杆菌是鱼类、牛和人类的重要病原体。例如在研究牛抗菌肽Bactenecin 5 (Bac5)时，发现它具有广泛的杀菌能力 。
其衍生物也表现出不同程度的抗菌活性。如合成的抗菌肽Bactenecin的两个衍生物，12个残基的肽Bac2a和8个残基的肽Bac8c，Bac2a对革兰氏阴性菌和革兰氏阳性菌的最低抑菌浓度（MIC）为2至32μM，而Bac8c表现出更大的抗菌活性 。
2、与传统抗菌物质对比的优势

传统抗生素在长期使用过程中，细菌容易产生耐药性。而Bactenecin作为抗菌肽，其作用机制与传统抗生素有所不同。普遍认为，抗菌肽通过膜损伤机制，破坏微生物细胞膜或细胞壁的完整性，达到抑杀微生物的目的。不过，越来越多的证据表明抗菌肽还存在非膜损伤机制，作用于胞内靶位点杀伤细胞。这种独特的作用机制使得细菌不易对其产生耐药性，在对抗耐药菌株方面具有很大的潜力，被视为传统抗生素或化学物质的潜在替代品。 
Bactenecin的应用领域
1、在医学领域的应用潜力

感染性疾病的治疗：由于其抗菌活性，Bactenecin可能用于治疗由细菌引起的感染性疾病。例如，在肠道细菌感染方面，有实验构建抗菌肽Bactenecin 7的重组质粒，并将其转化到乳酸乳球菌MG1363中，结果表明携Bactenecin7基因的乳酸菌能有效分泌表达具有生物活性的抗菌肽Bactenecin7，这为口服重组乳酸菌进行肠道细菌感染的治疗奠定了基础 。随着耐药菌问题的日益严重，Bactenecin这种具有独特抗菌机制的物质有望成为新的治疗药物。
免疫调节方面：Bactenecin还可能具有免疫调节潜力。如研究中的牛AMP Bactenecin 5 (Bac5)就展示了免疫调节潜力，这在机体对抗感染等过程中具有重要意义。通过调节免疫反应，可以帮助机体更好地应对病原体的侵袭，同时避免过度的免疫反应对自身组织造成损伤。
2、在农业领域的潜在应用

畜牧业中的应用：在牛等家畜养殖中，Bactenecin相关的抗菌肽可能有助于预防和治疗家畜的细菌感染性疾病。由于其对分枝杆菌等病原体的抗菌活性，能够减少这些病原体对家畜健康的威胁，从而提高畜牧业的生产效益。
水产养殖中的应用：考虑到Bactenecin对某些鱼类病原体有抗菌活性，它可能被应用于水产养殖中，用来控制鱼类疾病的发生和传播，保障水产养殖的健康发展。
Bactenecin相关实验案例
1、环状和线性Bactenecin的对比实验

在研究Bactenecin（一种来自牛中性粒细胞的12个氨基酸的阳离子抗菌肽）时，为了研究其二硫键的重要性，制造了线性衍生物Bac2S，并将还原形式（线性Bactenecin）也纳入研究。结果发现，Bactenecin对革兰氏阴性野生型细菌大肠杆菌、铜绿假单胞菌和鼠伤寒沙门氏菌的活性比其线性衍生物和还原形式更高，而这三种肽对前两种细菌的外膜屏障缺陷突变体的活性相同 。这个实验有助于深入了解Bactenecin的结构与抗菌活性之间的关系，为进一步改造和优化Bactenecin提供了依据。
2、Bactenecin衍生物的活性和机制研究实验

设计并合成了六种Bactenecin衍生物（如L2C3V10C11，RLCRIVVIRVCR）。随着多药耐药细菌的出现，抗菌肽被视为传统抗生素或化学物质的潜在替代品，这个实验旨在研究这些衍生物的生物活性和作用机制，以探索Bactenecin及其衍生物在应对耐药菌方面的潜力 。
3、Bactenecin短肽三苯基磷类似物实验

在研究抗菌肽（AMP）作为能够对抗耐药菌株的有前途的抗菌剂时，采用了一种方法，包括将与bactenecin 7 (Bac7)和oncocin (Onc112)序列相关的肽与烷基（三苯基）鏻 (烷基 - TPP)片段缀合，以改善AMP性能并引入新的AMP，扩大抗菌谱。这一实验探索了Bactenecin在构建新型抗菌剂方面的可能性，为开发更有效的抗菌药物提供了思路 。

Definition

Bacterial peptides are protein fragments which are either part of a bacterium or produced by a bacteria1.

Classification

Different classes of peptides are produced by bacteria. Some examples include, antibiotics, enterotoxins, flagellar proteins, lipoproteins and various enzymes1.

Structural Characteristics

Structural characteristics of some bacterial peptides are described below-

A)      Malaria merozoite surface peptide (MSP-1): It is synthesized as a large precursor on the surface of the bacterium Plasmodium falciparum.  Proteolytic cleavage results in the production of a 19 KDa product whose tertiary structure is maintained by disulphide bridges2.

B)     Giardia variable surface protein: This peptide is the specific conserved region of the Giardia variable surface proteins (VSPs) that are cysteine rich zinc finger proteins. VSPs differ in size and sequence, they are characterized by this highly conserved C-terminal membrane spanning region, a hydrophilic cytoplasmic tail with a conserved five amino acid CRGKA signature sequence3,4.

C)    P.falciparum liver stage antigen 3: The protein is 200Kda and is highly conserved among parasites from different geographic regions5.

Mode of action

A)     MSP-1 is known to trigger antibody response by CD4 helper T cells. It is likely that these cells bind to the C-terminal domain of MSP-12.

B)     VSPs have a conserved hydrophilic amono acid trail that is palmitoyted by palmityl tranferases upon which they are activated3,4.

C)    P. falciparum liver stage antigen 3 is a potent antigen that is recongnized by T cells5.

Functions

A)     MSP-1 is a vaccine candidate for Plasmodium falciparum infection. It triggers a CD-4 T cell response2.

B)     VSPs are necessary for survival in the environment and host infection3,4.

C)    P.falciparum stage antigen 3 is also a good candidate vaccine as it activates both T and B cell responses5.

References

1.     Gitai Z (2005). "The new bacterial cell biology: moving parts and subcellular architecture". Cell, 120 (5): 577–86.

2.     Stuart JQ and Jean L (2001). Different regions of the malaria merozoite surface protein 1 of Plasmodium chabaudi elicit distinct T-cell and antibody isotype responses. Infect Immun, 69(4): 2245–2251.

3.     Davids BJ, Reiner DS, Birkeland SR, Preheim SP, Cipriano MJ, McArthur AG, Gillin FD (2006). A New Family of Giardial Cysteine-Rich Non-VSP Protein Genes and a Novel Cyst Protein. PLoS ONE, 20,1:e44.

4.     Touz MC, Conrad JT, Nash TE (2005). A novel palmitoyl acyl transferase controls surface protein palmitoylation and cytotoxicity in Giardia lamblia. Mol Microbiol., 58 (4), 999-1011.

5.     Jean-Pierre S, Blanca LP, Karima B, Pierra D, Pierra D (2001). DNA Immunization by Plasmodium falciparum liver-stage antigen 3 induces protection against Plasmodium yoelii Sporozoite challenge. Infect Immun., 69, 1202–1206.

二硫键广泛存在与蛋白结构中，对稳定蛋白结构具有非常重要的意义，二硫键一般是通过序列中的2个Cys的巯基，经氧化形成。
 

形成二硫键的方法很多：空气氧化法，DMSO氧化法，过氧化氢氧化法等。
 

二硫键的合成过程，  可以通过Ellman检测以及HPLC检测方法对其反应进程进行监测。  
   

如果多肽中只含有1对Cys，那二硫键的形成是简单的。多肽经固相或液相合成，然后在pH8-9的溶液中进行氧化。      
 

当需要形成2对或2对以上的二硫键时，合成过程则相对复杂。尽管二硫键的形成通常是在合成方案的最后阶段完成，但有时引入预先形成的二硫化物是有利于连合或延长肽链的。通常采用的巯基保护基有trt, Acm, Mmt, tBu, Bzl, Mob, Tmob等多种基团。我们分别列出两种以2-Cl树脂和Rink树脂为载体合成的多肽上多对二硫键形成路线：
 

二硫键反应条件选择    
 

 二硫键即为蛋白质或多肽分子中两个不同位点Cys的巯基（-SH）被氧化形成的S-S共价键。 一条肽链上不同位置的氨基酸之间形成的二硫键，可以将肽链折叠成特定的空间结构。多肽分 子通常分子量较大，空间结构复杂，结构中形成二硫键时要求两个半胱氨酸在空间距离上接近。 此外，多肽结构中还原态的巯基化学性质活泼，容易发生其他的副反应，而且肽链上其他侧链 也可能会发生一系列修饰，因此，肽链进行修饰所选取的氧化剂和氧化条件是反应的关键因素， 反应机理也比较复杂，既可能是自由基反应，也可能是离子反应。      

反应条件有多种选择，比如空气氧化，DMSO氧化等温和的氧化过程，也可以采用H2O2，I2， 汞盐等激烈的反应条件。
 

空气氧化法： 空气氧化法形成二硫键是多肽合成中最经典的方法，通常是将巯基处于还原态的多肽溶于水中，在近中性或弱碱性条件下（PH值6.5-10），反应24小时以上。为了降低分子之间二硫键形成的可能，该方法通常需要在低浓度条件下进行。
 

碘氧化法：将多肽溶于25%的甲醇水溶液或30%的醋酸水溶液中，逐滴滴加10-15mol/L的碘进行氧化，反应15-40min。当肽链中含有对碘比较敏感的Tyr、Trp、Met和His的残基时，氧化条件要控制的更精确，氧化完后，立即加入维生素C或硫代硫酸钠除去过量的碘。 当序列中有两对或多对二硫键需要成环时，通常有两种情况：
 

自然随机成环:       序列中的Cys之间随机成环，与一对二硫键成环条件相似；
 

定点成环：       定点成环即序列中的Cys按照设计要求形成二硫键，反应过程相对复杂。在 固相合成多肽之前，需要提前设计几对二硫键形成的顺序和方法路线，选择不同的侧链 巯基保护基，利用其性质差异，分步氧化形成两对或多对二硫键。       通常采用的巯基保护 基有trt, Acm, Mmt, tBu, Bzl, Mob, Tmob等多种基团。

抗菌肽介绍一

AMPs是由相对较小的分子组成的异质基团，通常含有不到100个氨基酸。 它们最初是在20世纪60年代由Zeya和Spitznagel 在多形核白细胞溶酶体中描述的。 迄今为止，已在数据库（如数据库）中 确定和登记了2600多个AMP。  它们是由几乎所有的生物群产生的，包括细菌、真菌、植物和动物。 许多脊椎动物AMPs是由上皮表面分泌的，如 哺乳动物的气管、舌、肠粘膜或两栖动物的皮肤。 有些在中性粒细胞、单核 细胞和巨噬细胞中表达。 AMPs参与动物和植物的免疫防御系统。 构成表达或诱导它们在抵御微生物入侵者 的第一道防线中起着关键作用。

结构/分类 AMPs可以根据其氨基酸组成和结构进行分类。 可以区分两大类AMP。

第一类由线性分子组成，它们要么倾向于采用α螺旋结构，要么富含精氨酸、甘氨 酸、组氨酸、脯氨酸和色氨酸等某些氨 基酸。

第二类由含半胱氨酸的肽组成， 可分为单一或多个二硫结构。 在许多情 况下，抗菌活性需要存在二硫桥。 大多数AMPs是阳离子肽，但也有阴离子肽，如真皮素，一种富含天冬氨酸 的人肽和两栖动物的最大蛋白H5皮肤。 其他非阳离子AMPs包括神经肽前体分子的片段，如原啡肽A， 芳香二肽主要从二翅目幼虫中分离出来，或从节肢动物或茴香物种的氧结合 蛋白中提取的肽。

专肽生物可定制合成各类序列的抗菌肽，可标记FITC/FAM/TAMRA等常见荧光素。

Definition

Antimicrobial peptides (AMPs) are as widespread as bacterial inactivator molecules in the innate immune systems of insects, fungi, plants, and mammals. These peptides are also known as host defense peptides (HDPs) as they have other immuno-modulatory functions besides the direct antimicrobial actions and are even capable of killing cancerous cells 1,2. 

Classification

Three broad categories of HDPs have been identified: 1) the linear peptides with helical structures, 2) the cysteine stabilized peptides with beta-sheet, and 3) a group of linear peptides rich in proline and arginine that primarily have been identified in non-mammalian species. 

Structural characteristics

In mammals, cathelicidins and defensins are the two principal AMP families. Cathelicidins are peptides with a conserved proregion and a variable C-terminal antimicrobial domain. Defensins are the best-characterized AMPs, they have six invariant cysteines, forming three intramolecular cystine-disulfide bonds. 

Mode of action

The mode of action of AMPs elucidated to date include inhibition of cell wall formation, formation of pores in the cell membrane resulting in the disruption of membrane potential with eventual lysis of the cell. These peptides also inhibit nuclease activity of both RNase and DNase. 

Functions

They have a broad ability to kill microbes. AMPs form an important means of host defense in eukaryotes. Large AMPs (>100 amino acids), are often lytic, nutrient-binding proteins or specifically target microbial macromolecules. Small AMPs act by disrupting the structure of microbial cell membranes. It plays an active role in wound repair and regulation of the adaptive immune system. They have multiple roles as mediators of inflammation with impact on epithelial and inflammatory cells, influencing diverse processes such as cell proliferation, wound healing, cytokine release, chemotaxis and  immune induction 3. 

References 

1.     Gottlieb CT, Thomsen LE, Ingmer H, Mygind PH, Kristensen HH, Gram L(2008). Antimicrobial peptides effectively kill a broad spectrum of Listeria monocytogenes and Staphylococcus aureus strains independently of origin, sub-type, or virulence factor expression. BMC Microbiol., 8:205.

2.     Yeaman MR and Yount NY (2003). Mechanisms of Antimicrobial Peptide Action and Resistance.  Pharmocological Reviews, 55(1).

3.     Hanna Galkowska H and Olszewski WL (2003). Antimicrobial peptides – their role in immunity and therapeutic potential. Centr Eur J Immunol., 28 (3):138–141.

抗菌肽介绍二

Ribosomally synthesized antimicrobial peptides (AMPs) constitute a structurally diverse group of molecules found virtually in all organisms. Most antimicrobial peptides contain less than 100 amino acid residues, have a net positive charge, and are membrane active. They are major players in the innate immune defense but can also have roles in processes as chemokine induction, chemotaxis, inflammation, and wound healing. In addition to their antimicrobial effects, many of them show antiviral and antineoplastic activities.

INTRODUCTION
AMPs are a heterogeneous group of relatively small molecules usually containing less than a hundred amino acids. They were first described in the 1960’s by Zeya and Spitznagel in polymorphonuclear leukocyte lysosomes.

To date, more than 2600 AMPs have been identified and registered in databases. They are produced by nearly all groups of organisms, including bacteria, fungi, plants, and animals. Many vertebrate AMPs are secreted by epithelial surfaces such as the tracheal, lingual, or intestinal mucosa of mammals or the skin of amphibia. Some are expressed in neutrophils, monocytes, and macrophages.

AMPs are involved in both animal and plant immune defense systems. Constitutively expressed or induced they play a key role in the first line of defense against microbial intruders.

STRUCTURE/CLASSIFICATION
AMPs can be classified on the basis of their amino acid composition and structure. Two major groups of AMPs can be distinguished. The first group consists of linear molecules which either tend to adopt α-helical structure or are enriched in certain amino acids such as arginine, glycine, histidine, proline, and tryptophan. The second group consists of cysteine-containing peptides which can be divided into single or multiple disulfide structures. In many cases, the presence of disulfide bridges is required for antimicrobial activity.

Most AMPs are cationic peptides, but there are also anionic peptides such as dermcidin, an aspartic acid-rich peptide from human and maximin H5 from amphibian skin. Other non-cationic AMPs include fragments from neuropeptide precursor molecules such as proenkephalin A, aromatic dipeptides primarily isolated from dipteran larvae, or peptides derived from oxygen-binding proteins from arthropod or annelid species.

MODE OF ACTION
Most AMPs act by provoking an increase in plasma membrane permeability. They preferentially target microbial versus mammalian cells. Selectivity is influenced by several factors such as differences in membrane composition: membranes of many bacterial pathogens contain negatively charged lipid moieties such as phosphatidylglycerol (PG), cardiolipin, and phosphatidylserine (PS), whereas mammalian membranes, commonly enriched in phosphatidylethanolamine (PE), phosphatidylcholine (PC) and sphingomyelin, are generally neutral in net charge.

The presence of sterols such as cholesterol and ergesterol within the membrane may be a further means by which AMPs can distinguish between mammalian or fungal cells and prokaryotes. A first step in the mechanism of membrane permeabilization is the electrostatic interaction between the positively charged AMP with the negatively charged membrane surface of the microorganism. Subsequent disruption of the membrane by creation of  pores within the microbial membrane ultimately results in cell death of the organism due to leakage of ions, metabolites, cessation of membrane-coupled respiration, and biosynthesis.

Several models for pore formation such as the Barrel-Stave, the Toroidal or Wormhole Model, and the Carpet Model have been proposed (Fig. 1).

FIG. 1. MODE OF ACTION A BARREL-STAVE MODEL B TOROIDAL PORE OR WORMHOLE MODEL C CARPET MODEL

THE BARREL-STAVE MODEL
The Barrel-Stave model describes a mechanism in which AMPs form a barrellike pore within the bacterial membrane with the individual AMPs or AMP complexes being the staves. Arranged in this manner, the hydrophobic regions of the AMPs point outwards towards the acyl chains of the membrane whereas the hydrophilic areas form the pore.

THE TOROIDAL PORE OR WORMHOLE MODEL
The pores described by this model differ from those of the Barrel-Stave model. Primarily, the outer and inner leaflet of the membrane are not intercalated in the transmembrane channel.

THE CARPET MODEL
A different mechanism is proposed in the Carpet model where AMPs first cover the outer surface of the membrane and then disrupt the membrane like detergents by forming micelle-like units. Certain AMPs penetrate the bacterial membrane without channel formation. They act on intracellular targets by e.g. inhibiting nucleic acid and/or protein synthesis.

RESISTANCE
Resistance to AMPs can either be constitutive or inducible. Inherited resistance mechanisms include altered surface charge, active efflux, production of peptidases or trapping proteins, and modification of host cellular processes. For instance, Staphylococcus aureus manages to reduce the overall cell surface charge by esterification of the cell wall component teichoic acid with D-alanine and thereby increases its resistance against human AMPs. Another example for changing the surface net charge is the production of cationic lysine-substituted phosphatidylglycerol (L-PG) found in certain Staphylococcus aureus strains. In Gram-negative bacteria, addition of 4-aminoarabinose (Ara4N) to the phosphate group of the lipid A backbone or increased acylation of lipopolysaccharides (LPS) are important mechanisms of AMP resistance. Exposure to AMPs may also induce stress responses by which microorganisms try to survive. Inducible regulatory mechanisms have been described in a variety of organisms. For instance, the PhoP/PhoQ regulon in Salmonella has been demonstrated to regulate transcriptional activation of surface and secretory proteins, enzymes that modify lipopolysaccharide, lipid and protein constituents of the outer membrane and proteases that likely degrade certain AMPs.

EXAMPLES OF ANTIMICROBIAL PEPTIDES

ADAPTED FROM K.A. BROGDEN, NAT. REV. MICROBIOL. 3, 238-250 (2005)

IMPORTANT FAMILIES OF AMPS
BOMBININS
Bombinins constitute a family of AMPs produced in fire-bellied toads (Bombina species) active against Gram-negative and Gram-positive bacteria and fungi. Bombinins, bombinin-like peptides (BLPs), and Bombinin H molecules are found in the species Bombina bombina, Bombina variegata, and Bombina orientalis, whereas the homologous maximins and maximin H peptides are derived from the giant fire-bellied toad Bombina maxima. Bombinin H peptides contain either 17 or 20 amino acid residues and are more hydrophobic than bombinins, some of them contain D-alloisoleucine at position 2. They exhibit lower antibacterial activity than bombinins but, in contrast to them, they possess haemolytic activity.

CATHELICIDINS
Members of this family are amphipathic, cationic peptides with a broad-spectrum antimicrobial activity. Cathelicidins typically act by disrupting the integrity of bacterial membranes. They are characterized by an evolutionary conserved N-terminal cathelin- like domain of approximately 99-114 amino acid residues linked to a C-terminal antimicrobial domain of 12-100 residues that can be released upon proteolytic processing. Members of this family include linear peptides amongst them a number of proline-rich AMPs that show different types of proline repeat motifs (Bac5, Bac7, PR-39, prophenins) and the tryptophan-rich indolicidin characterized by three regularly spaced proline residues. The protegrins (PG-1 to PG-5) contain two disulfide bridges and an amidated C-terminus. Cathelicidins have been found in every mammalian species examined. In human, LL-37 (Product 4042456) is the only member of the cathelicidin family. The peptide consists of 37 amino acids and contains two leucine residues at the N-terminus. It is proteolytically cleaved from the 18 kDa precursor protein human cathelicidin antimicrobial protein CAP-18. LL-37 is primarily produced by phagocytic leucocytes and epithelial cells, and is involved in various processes such as direct killing of microorganisms, binding and neutralizing LPS, chemotaxis and chemokine induction, regulation of inflammatory responses, and wound healing. Its production is influenced by several factors such as microbial products, host cytokines, vitamin D3, and availability of oxygen. LL-37 orthologues in mouse and rat are CRAMP (mouse) (Product 4056438) and CRAMP (rat), respectively.

CECROPINS
Cecropins were first isolated from the giant silk moth Hyalophora cecropia. They can form amphipathic, α-helical structures and are structurally related to other cecropins as bactericidin, lepidopteran, and sarcotoxin. Cecropin P1 (Product 4039862), found in pig intestine, also belongs to this family. Most cecropins show broad-spectrum antibacterial activity. Cecropin A (Product 4030488) and B (Product 4030477) have also been demonstrated to possess tumoricidal activity against mammalian leukemia, lymphoma, and carcinoma cell lines.

CERATOTOXINS
This family consists of cationic α-helical amphipathic peptides expressed in the female reproductive accessory glands of the Mediterranean fruit fly Ceratitis capitata. The production of the peptides is enhanced by mating. Ceratotoxin A and ceratotoxin B are 29 amino acid peptides differing in two amino acids. Ceratotoxin C and D consist of 32 and 36 amino acids, respectively. The peptides of this family are active against Gram-negative as well as Grampositive bacteria and are supposed to act via the Barrel-Stave model. Ceratotoxin A has been shown to be mainly antibacterial for Gram-negative organisms.

DEFENSINS
Defensins are small cysteine-rich cationic peptides containing three or four disulfide bridges. They have been isolated from molluscs, acari, arachnids, insects, mammals, and plants. They are further divided into families on the basis of the spatial distribution of their cysteine residues. Three families, the α-, β- and θ-defensins, can be distinguished in mammals. α- and β-defensins are characterized by antiparallel β-sheet structures stabilized by three disulfide bonds. The θ-defensins are found in rhesus monkey and some other non-human primates but not in human, chimpanzee and gorilla. They consist of two nine amino acid peptides derived from different precursor proteins joined by head-to-tail cyclization. Invertebrate and plant defensins contain three or four disulfide  bridges, respectively. Insect and mammalian defensins are mainly active against bacteria while most plant defensins possess antifungal activity.

DERMASEPTINS
The peptides of the dermaseptin family are closely related and consist of 28-34 amino acids. They were originally isolated from skin extracts of the South American arboreal frog Phyllomedusa sauvagei and contain a conserved tryptophan residue at position 3. Dermaseptins exhibit broad-spectrum antimicrobial activity against Gram-positive and Gram-negative bacteria.

HISTATINS
Histatins are histidine-rich and mostly cationic peptides found in the saliva of humans and some higher primates. They are active against a broad-spectrum of bacteria and fungi. The antifungal activity of the human salivary peptide histatin-5 has been extensively studied and is supposed to be due to inhibition of mitochondrial respiration and the formation of reactive oxygen species. Histatin-5 has also been shown to inhibit both host-derived and bacterial proteolytc enzymes involved in peridontal diseases. Histatin-8, a peptide from human parotid secretion, has been shown to inhibit hemagglutination activity of Porphyromonas gingivalis 381, a Gram-negative bacterium involved in certain forms of periodontal disease. The peptide may function as a binding domain for the hemagglutinins of Porphyromonas gingivalis during agglutination.

MAGAININS
Magainins constitute a family of linear amphipathic cationic AMPs discovered in the skin of Xenopus laevis. The two closely related members of this family, magainin I (Product 4012844) and magainin II (Product 4013706) differ merely in two positions and are 23 amino acids in length. Magainins exhibit broad-spectrum antimicrobial activity against Gram-negative and Gram-positive bacteria, fungi and protozoa and are also cytotoxic for many murine and human cancer cell lines.

CONCLUSIONS
The structures of AMPs represent a unique source for the targeted exploration of new applications in the therapy of microbial and viral infection, cancer, and sepsis. Modern synthetic methods will allow the relatively cheap and accurate production of lead compounds and peptide candidates. The achievements in peptide library generation, analytical methods as mass spectrometry, and screening and formulation technologies may contribute to solve intrinsic problems associated with the use of AMPs as therapeutic agents such as susceptibility to proteases and host toxicity. Bachem has considerable expertise and long-standing experience in peptide synthesis. With our capacity to upscale the production of simple and modified peptides, we are the partner of choice for the pharmaceutical industries.