[신간의 별자리x] 우리/미술, 그리고 ‘슬픔의 박물관’

The expanding scope of antimicrobial peptide structures and their modes of action.

Background
The amyloid β-protein (Aβ) is believed to be the key mediator of Alzheimer's disease (AD) pathology. Aβ is most often characterized as an incidental catabolic byproduct that lacks a normal physiological role. However, Aβ has been shown to be a specific ligand for a number of different receptors and other molecules, transported by complex trafficking pathways, modulated in response to a variety of environmental stressors, and able to induce pro-inflammatory activities.

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The Alzheimer's Disease-Associated Amyloid β-Protein Is an Antimicrobial Peptide

Antibiotic resistance is projected as one of the greatest threats to human health in the future and hence alternatives are being explored to combat resistance. Antimicrobial peptides (AMPs) have shown great promise, because use of AMPs leads bacteria to develop no or low resistance. In this review, we discuss the diversity, history and the various mechanisms of action of AMPs. Although many AMPs have reached clinical trials, to date not many have been approved by the US Food and Drug Administration (FDA) due to issues with toxicity, protease cleavage and short half-life. Some of the recent strategies developed to improve the activity and biocompatibility of AMPs, such as chemical modifications and the use of delivery systems, are also reviewed in this article.

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Antimicrobial Peptides: Diversity, Mechanism of Action and Strategies to Improve the Activity and Biocompatibility In Vivo

Life-threatening infectious diseases are on their way to cause a worldwide crisis, as treating them effectively is becoming increasingly difficult due to the emergence of antibiotic resistant strains. Antimicrobial peptides (AMPs) form an ancient type of innate immunity found universally in all living organisms, providing a principal first-line of defense against the invading pathogens. The unique diverse function and architecture of AMPs has attracted considerable attention by scientists, both in terms of understanding the basic biology of the innate immune system, and as a tool in the design of molecular templates for new anti-infective drugs. AMPs are gene-encoded short (<100 amino acids), amphipathic molecules with hydrophobic and cationic amino acids arranged spatially, which exhibit broad spectrum antimicrobial activity. AMPs have been the subject of natural evolution, as have the microbes, for hundreds of millions of years. Despite this long history of co-evolution, AMPs have not lost their ability to kill or inhibit the microbes totally, nor have the microbes learnt to avoid the lethal punch of AMPs. AMPs therefore have potential to provide an important breakthrough and form the basis for a new class of antibiotics. In this review, we would like to give an overview of cationic antimicrobial peptides, origin, structure, functions, and mode of action of AMPs, which are highly expressed and found in humans, as well as a brief discussion about widely abundant, well characterized AMPs in mammals, in addition to pharmaceutical aspects and the additional functions of AMPs.

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Antimicrobial peptides: key components of the innate immune system

Anionic antimicrobial peptides / proteins (AAMPs) were first reported in the early 1980s and since then, have been established as an important part of the innate immune systems of vertebrates, invertebrates and plants. These peptides are active against bacteria, fungi, viruses and pests such as insects. AAMPs may be induced or expressed constitutively and in some cases, antimicrobial activity appears to be a secondary role for these peptides with other biological activities constituting their primary role. Structural characterization shows AAMPs to generally range in net charge from -1 to -7 and in length from 5 residues to circa 70 residues and for a number of these peptides, post-translational modifications are essential for antimicrobial activity. Membrane interaction appears key to the antimicrobial function of AAMPs and to facilitate these interactions, these peptides generally adopt amphiphilic structures. These architectures vary from the alpha-helical peptides of some amphibians to the cyclic cystine knot structures observed in some plant proteins. Some AAMPs appear to use metal ions to form cationic salt bridges with negatively charged components of microbial membranes, thereby facilitating interaction with their target organisms, but in many cases, the mechanisms underlying the antimicrobial action of these peptides are unclear or have not been elucidated. Here, we present an overview on current research into AAMPs, which suggests that these peptides are an untapped source of putative antimicrobial agents with novel mechanisms of action and possess potential for application in the medical and biotechnological arenas.

Anionic Antimicrobial Peptides from Eukaryotic Organisms

Cancer is a major cause of premature death and there is an urgent need for new anticancer agents with novel mechanisms of action. Here we review recent studies on a group of peptides that show much promise in this regard, exemplified by arthropod cecropins and amphibian magainins and aureins. These molecules are alpha-helical defence peptides, which show potent anticancer activity (alpha-ACPs) in addition to their established roles as antimicrobial factors and modulators of innate immune systems. Generally, alpha-ACPs exhibit selectivity for cancer and microbial cells primarily due to their elevated levels of negative membrane surface charge as compared to non-cancerous eukaryotic cells. The anticancer activity of alpha-ACPs normally occurs at micromolar levels but is not accompanied by significant levels of haemolysis or toxicity to other mammalian cells. Structure/function studies have established that architectural features of alpha-ACPs such as amphiphilicty levels and hydrophobic arc size are of major importance to the ability of these peptides to invade cancer cell membranes. In the vast majority of cases the mechanisms underlying such killing involves disruption of mitochondrial membrane integrity and/or that of the plasma membrane of the target tumour cells. Moreover, these mechanisms do not appear to proceed via receptor-mediated routes but are thought to be effected in most cases by the carpet/toroidal pore model and variants. Usually, these membrane interactions lead to loss of membrane integrity and cell death utilising apoptic and necrotic pathways. It is concluded that that alpha-ACPs are major contenders in the search for new anticancer drugs, underlined by the fact that a number of these peptides have been patented in this capacity.

Anticancer α-Helical Peptides and Structure / Function Relationships Underpinning Their Interactions with Tumour Cell Membranes

To facilitate microbial membrane invasion, amphiphilic α-helical antimicrobial peptides (α-AMPs) show a spatial segregation of hydrophobic and hydrophilic residues about the α-helical long axis. Here we discuss potential mechanisms by which these peptides are able to disrupt membrane structure and the structural characteristics, which are required for function.

https://amit1b.files.wordpress.com/2008/03/dennison-2005-structure-function-in-amphipathic-amps.pdf

Amphiphilic α-Helical Antimicrobial Peptides and Their Structure / Function Relationships

Here, we review potential determinants of the anticancer efficacy of innate immune peptides (ACPs) for cancer cells. These determinants include membrane-based factors, such as receptors, phosphatidylserine, sialic acid residues, and sulfated glycans, and peptide-based factors, such as residue composition, sequence length, net charge, hydrophobic arc size, hydrophobicity, and amphiphilicity. Each of these factors may contribute to the anticancer action of ACPs, but no single factor(s) makes an overriding contribution to their overall selectivity and toxicity. Differences between the anticancer actions of ACPs seem to relate to different levels of interplay between these peptide and membrane-based factors.

On the selectivity and efficacy of defense peptides with respect to cancer cells.

PACT therapy involves the use of a chemical dye which targets the organism cell wall, in this case the fungus. The dye is activated by a high powered lamp which starts a chemical reaction, and the release of oxygen into the affected nail plate. This sudden and prolonged release of oxygen helps to destroy the cell wall of the fungus and over the course of your treatment helps to eradicate it from your nail plate.

Sarah R. Dennison

Papers

Anionic Antimicrobial Peptides from Eukaryotic Organisms

Anticancer α-Helical Peptides and Structure / Function Relationships Underpinning Their Interactions with Tumour Cell Membranes

Amphiphilic α-Helical Antimicrobial Peptides and Their Structure / Function Relationships

On the selectivity and efficacy of defense peptides with respect to cancer cells.

Photodynamic Antimicrobial Chemotherapy