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1.
Due to the rapid emergence of resistant microbes to the currently available antibiotics, cationic antimicrobial peptides have
attracted considerable interest as a possible new generation of anti-infective compounds. However, low cost development for
therapeutic or industrial purposes requires, among other properties, that the peptides will be small and with simple structure.
Therefore, considerable research has been devoted to optimizing peptide length combined with a simple design. This review
focuses on the similarities and differences in the mode of action and target cell specificity of two families of small peptides:
the naturally occurring temporins from the skin of amphibia and the engineered ultrashort lipopeptides. We will also discuss
the finding that acylation of cationic peptides results in molecules with a more potent spectrum of activity and a higher
resistance to proteolytic degradation. Conjugation of fatty acids to linear native peptide sequences is a powerful strategy
to engineer novel successful anti-infective drugs. 相似文献
2.
Anti herpes simplex virus activity of lactoferrin/lactoferricin – an example of antiviral activity of antimicrobial protein/peptide 总被引:3,自引:0,他引:3
Jenssen H 《Cellular and molecular life sciences : CMLS》2005,62(24):3002-3013
One of the most common viral infections in humans is caused by the herpes simplex virus (HSV). It was first effectively treated
in the 1970s with the introduction of acyclovir, which is still the most commonly used treatment. Naturally occurring antimicrobial
proteins and peptides have also been shown to possess antiviral activity against HSV. This review will focus on the anti-HSV
activity of one such protein, lactoferrin, and a small peptide fragment from its N-terminal domain, lactoferricin. Both components
have been shown to effectively block entry of HSV into the host cell. In addition to blocking HSV entry, the peptides appear
to have immune stimulatory activity, although this is still somewhat controversial. Mode of action studies and knowledge about
the anti-HSV activity of lactoferricin have also been successfully employed in the design of new, more specific HSV blockers.
Received 25 May 2005; received after revision 24 August 2005; accepted 6 September 2005 相似文献
3.
Cationic host defence peptides: Innate immune regulatory peptides as a novel approach for treating infections 总被引:9,自引:0,他引:9
An increase in antibiotic resistance and the emergence of new pathogens has led to an urgent need for alternative approaches
to infection management. Immunomodulatory molecules that do not target the pathogen directly, but rather selectively enhance
and/or alter host defence mechanisms, are attractive candidates for therapeutic development. Natural cationic host defence
peptides represent lead molecules that boost innate immune responses and selectively modulate pathogen-induced inflammatory
responses. This review discusses recent evidence exploring the mechanisms of cationic host defence peptides as innate immune
regulators, their role in the interface of innate and adaptive immunity, and their potential application as beneficial therapeutics
in overcoming infectious diseases.
Received 3 November 2006; received after revision 14 December 2006; accepted 22 January 2007 相似文献
4.
Delivery of macromolecules into living cells by arginine-rich cell penetrating peptides (AR-CPPs) is an important new avenue
for the development of novel therapeutic strategies. However, to date the mechanism of this delivery remains elusive. Recent
data implicate endocytosis in the internalization of AR-CPPs and their macromolecular cargo and also indicate limited delivery
of macromolecules into the cell cytoplasm and nucleus. Different types of endocytosis – clathrin-dependent endocytosis, raft/caveolin-dependent
endocytosis and macropinocytosis – are all implicated in the uptake of AR-CPPs and their cargo into different cells. Cationic
AR-CPPs dramatically increase uptake of conjugated molecules through efficient binding to surface proteoglycans. Whether this
increase in binding can assure delivery of a sufficient amount of functionally active macromolecules into the cytoplasm and
nucleus or whether there is a specific mechanism by which AR-CPPs facilitate the escape of conjugated cargo from endosomes
remains to be understood.
Received 30 June 2005; received after revision 9 August 2005; accepted 30 August 2005 相似文献
5.
Plasticins belong to the dermaseptin superfamily of gene-encoded, membrane-active host defense peptides produced by the skin
of hylid frogs. The plasticins, which are rich in Gly and Leu residues arranged in regular 5-mer motifs GXXXG (where X is
any amino acid residue), have very similar amino acid sequences, hydrophobicities, and amphipathicities but differ markedly
in their net charge, conformational plasticity, and activity spectra. The intrinsic flexibility and structural malleability
of plasticins modulate their ability to bind to and disrupt the membranes of prokaryotic and eukaryotic cells, and/or to reach
intracellular targets, therefore triggering functional versatility. This family of closely related but functionally divergent
peptides constitutes a good model to address the relationships between structural polymorphism, membrane-interacting properties,
and the biological activity of antimicrobial, cell-penetrating, and viral fusion peptides. Plasticins could thus serve as
templates to design potent multifunctional drugs that could act simultaneously against bacterial pathogens and viruses.
Received 26 September 2007; received after revision 22 October 2007; accepted 29 October 2007 相似文献
6.
Stec B 《Cellular and molecular life sciences : CMLS》2006,63(12):1370-1385
Thionins belong to a rapidly growing family of biologically active peptides in the plant kingdom. Thionins are small (∼5 kDA),
cysteine-rich peptides with toxic and antimicrobial properties. They show a broad cellular toxicity against wide range of
organisms and eukaryotic cell lines; while possessing some selectivity. Thionins are believed to be involved in protection
against plant pathogens, including bacteria and fungi, by working directly at the membrane. The direct mechanism of action
is still surrounded by controversy. Here the results of structural studies are reviewed and confronted with recent results
of biophysical studies aimed at defining the function of thionins. The proposed toxicity mechanisms are reviewed and the attempt
to reconcile competing hypotheses with a wealth of structural and functional studies is made.
Received 3 December 2005; received after revision 6 February 2006; accepted 18 March 2006 相似文献
7.
Human skin is permanently exposed to microorganisms, but rarely infected. One reason for this natural resistance might be
the existence of a ‘chemical barrier’ consisting in constitutively and inducibly produced antimicrobial peptides and proteins
(AMPs). Many of these AMPs can be induced in vitro by proinflammatory cytokines or bacteria. Apart from being expressed in vivo in inflammatory lesions, some AMPs are also focally expressed in skin in the absence of inflammation. This suggests that
non-inflammatory stimuli of endogenous and/or exogenous origin can also stimulate AMP synthesis without inflammation. Such
mediators might be ideal ‘immune stimulants’ to induce only the innate antimicrobial skin effector molecules without causing
inflammation.
Received 9 August 2005; received after revision 21 October 2005; accepted 16 November 2005 相似文献
8.
The eye and its associated tissues including the lacrimal system and lids have evolved several defence mechanisms to prevent
microbial invasion. Included among this armory are several host-defence peptides. These multifunctional molecules are being
studied not only for their endogenous antimicrobial properties but also for their potential therapeutic effects. Here the
current knowledge of host-defence peptide expression in the eye will be summarised. The role of these peptides in eye disease
will be discussed with the primary focus being on infectious keratitis, inflammatory conditions including dry eye and wound
healing. Finally the potential of using host-defence peptides and their mimetics/derivatives for the treatment and prevention
of eye diseases is addressed. 相似文献
9.
Mukhopadhyay A Ni L Yang CS Weiner H 《Cellular and molecular life sciences : CMLS》2005,62(16):1890-1899
Phage display was used to identify new components of the mammalian mitochondrial receptor complex using Tom20 as a binding partner. Two peptides were identified. One had partial identity (SMLTVMA) with a bacterial signal peptide from Toho-1, a periplasmic protein. The other had partial identity with a mitochondrial inner membrane glutamate carrier. The bacterial signal peptide could carry a protein into mitochondria both in vivo and in vitro. The first six residues of the sequence, SMLTVM, were necessary for import but the two adjacent arginine residues in the 30-amino-acid leader were not critical for import. The signal peptides of Escherichia coli β-lactamase and Bacillsus subtilis lipase could not carry proteins into mitochondria. Presumably, the Toho-1 leader can adopt a structure compatible for recognition by the import apparatus.Received 29 April 2005; received after revision 8 June 2005; accepted 17 June 2005 相似文献
10.
Courtois G 《Cellular and molecular life sciences : CMLS》2005,62(15):1682-1691
The nuclear factor-κB (NF-κB) signaling pathway plays a key role in inflammation, immune response, cell growth control and protection against apoptosis. Recently, it has been associated with several distinct genetic diseases that exhibit a large spectrum of dysfunction, such as skin inflammation, perturbed skin appendage development and immunodeficiencies. In this review, a summary of the pathophysiological consequences of impaired NF-κB activation in humans is provided with respect to the functions of the molecules which are mutated.Received 26 January 2005; received after revision 7 March 2005; accepted 31 March 2005 相似文献
11.
Tollin M Bergsson G Kai-Larsen Y Lengqvist J Sjövall J Griffiths W Skúladóttir GV Haraldsson A Jörnvall H Gudmundsson GH Agerberth B 《Cellular and molecular life sciences : CMLS》2005,62(19-20):2390-2399
Vernix caseosa is a white cream-like substance that covers the skin of the foetus and the newborn baby. Recently, we discovered antimicrobial peptides/proteins such as LL-37 in vernix, suggesting host defence functions of vernix. In a proteomic approach, we have continued to characterize proteins in vernix and have identified 20 proteins, plus additional variant forms. The novel proteins identified, considered to be involved in host defence, are cystatin A, UGRP-1, and calgranulin A, B and C. These proteins add protective functions to vernix such as antifungal activity, opsonizing capacity, protease inhibition and parasite inactivation. The composition of the lipids in vernix has also been characterized and among these compounds the free fatty acids were found to exhibit antimicrobial activity. Interestingly, the vernix lipids enhance the antimicrobial activity of LL-37 in vitro, indicating interactions between lipids and antimicrobial peptides in vernix. In conclusion, vernix is a balanced cream of compounds involved in host defence, protecting the foetus and newborn against infection. 相似文献
12.
With the rapid rise in the emergence of bacterial strains resistant to multiple classes of antimicrobial agents, there is
an urgent need to develop novel antimicrobial therapies to combat these pathogens. Cationic host defence peptides (HDPs) and
synthetic derivatives termed innate defence regulators (IDRs) represent a promising alternative approach in the treatment
of microbial-related diseases. Cationic HDPs (also termed antimicrobial peptides) have emerged from their origins as nature’s
antibiotics and are widely distributed in organisms from insects to plants to mammals and non-mammalian vertebrates. Although
their original and primary function was proposed to be direct antimicrobial activity against bacteria, fungi, parasites and/or
viruses, cationic HDPs are becoming increasingly recognized as multifunctional mediators, with both antimicrobial activity
and diverse immunomodulatory properties. Here we provide an overview of the antimicrobial and immunomodulatory activities
of cationic HDPs, and discuss their potential application as beneficial therapeutics in overcoming infectious diseases. 相似文献
13.
Lisowska E 《Cellular and molecular life sciences : CMLS》2002,59(3):445-455
Glycosylation of proteins is a common event and contributes to protein antigenic properties. Most data have been obtained
from model studies on glycoprotens with well-defined structure or synthetic glycopeptides and their respective monoclonal
antibodies. Antibodies raised against glycoprotein antigens may be specific for their carbohydrate units which are recognized
irrespective of the protein carrier (carbohydrate epitopes), or in the context of the adjacent amino acid residues (glycopeptidic
epitopes). Conformation or proper exposure of peptidic epitopes of glycoproteins is also frequently modulated by glycosylation
due to intramolecular carbohydrate-protein interactions. The effects of glycosylation are broad: glycosylation may 'inactivate'
the peptidic epitope or may be required for its reactivity with the antibody, depending on the structure of the antigenic
site and antibody fine specificity. Evidence is increasing that similar effects of glycosylation pertain to T cell-dependent
cellular immune responses. Glycosylated peptides can be bound and presented by MHC class I or II molecules and elicit glycopeptide-specific
T cell clones.
Received 5 July 2001; received after revision 9 October 2001; accepted 11 October 2001 相似文献
14.
Nicole L. van der Weerden Mark R. Bleackley Marilyn A. Anderson 《Cellular and molecular life sciences : CMLS》2013,70(19):3545-3570
Antimicrobial peptides are a vital component of the innate immune system of all eukaryotic organisms and many of these peptides have potent antifungal activity. They have potential application in the control of fungal pathogens that are a serious threat to both human health and food security. Development of antifungal peptides as therapeutics requires an understanding of their mechanism of action on fungal cells. To date, most research on antimicrobial peptides has focused on their activity against bacteria. Several antimicrobial peptides specifically target fungal cells and are not active against bacteria. Others with broader specificity often have different mechanisms of action against bacteria and fungi. This review focuses on the mechanism of action of naturally occurring antifungal peptides from a diverse range of sources including plants, mammals, amphibians, insects, crabs, spiders, and fungi. While antimicrobial peptides were originally proposed to act via membrane permeabilization, the mechanism of antifungal activity for these peptides is generally more complex and often involves entry of the peptide into the cell. 相似文献
15.
Conlon JM 《Cellular and molecular life sciences : CMLS》2011,68(13):2303-2315
Cationic peptides that adopt an amphipathic α-helical conformation in a membrane-mimetic environment are synthesized in the
skins of many frog species. These peptides often display cytolytic activities against bacteria and fungi consistent with the
idea that they play a role in the host’s system of defense against pathogenic microorganisms, but their importance in the
survival strategy of the animal is not clearly understood. Despite the common misconception that antimicrobial peptides are
synthesized in the skins of all anurans, the species distribution is sporadic, suggesting that their production may confer
some evolutionary advantage to the organism but is not necessary for survival. The low potency of many frog skin antimicrobial
peptides is consistent with the hypothesis that cutaneous symbiotic bacteria may provide the major system of defense against
pathogenic microorganisms in the environment with antimicrobial peptides assuming a supplementary role in some species. 相似文献
16.
Small cationic antimicrobial peptides (SCAMPs) as effectors of animal innate immunity provide the first defense against infectious pathogens. This class of molecules exists widely in invertebrate hemolymph and vertebrate skin secretion, but animal venoms are emerging as a new rich resource. Scorpine is a unique scorpion venom defensin peptide that has an extended amino-terminal sequence similar to cecropins. From the African scorpion Opistophthalmus carinatus venom gland, we isolated and identified several cDNAs encoding four new homologs of scorpine (named opiscorpines 1–4). Importantly, we show for the first time the existence of multiple opiscorpine mRNAs with variable 3 untranslated regions (UTRs) in the venom gland, which may be generated by alternative usage of polyadenylation signals. The complete opiscorpine gene structure including its promoter region is determined by genomic DNA amplification. Two large introns were found to be located within the 5 UTR and at the boundary of the mature peptide-coding region. Such a gene structure is distinct, when compared with other scorpion venom peptide genes. However, a comparative promoter analysis revealed that both opiscorpine and scorpion venom neurotoxins share a similar promoter organization. Sequence analysis and structural modeling allow us to group the scorpines and scorpion long-chain K-channel toxins together into one family that shares a similar fold with two distinct domains. The N-terminal cecropin-like domain displaying a clear antimicrobial activity implies that the scorpine family represents a group of real naturally occurring hybrids. Based on the phylogenetic analysis, a possible cooperative interaction between the N and C domains is elucidated, which provides an evolutionary basis for the design of a new class of anti-infectious drugs.Received 5 April 2004; accepted 17 May 2004 相似文献
17.
The short proline-rich antibacterial peptide family 总被引:16,自引:0,他引:16
Otvos L 《Cellular and molecular life sciences : CMLS》2002,59(7):1138-1150
From the many peptide families that are induced upon bacterial infection and can be isolated from all classes of animals,
the short, proline-rich antibacterial peptides enjoy particular interest. These molecules were shown to inactivate an intracellular
biopolymer in bacteria without destroying or remaining attached to the bacterial cell membrane, and as such emerged as viable
candidates for the treatment of mammalian infections. These peptides were originally isolated from insects, they kill mostly
Gram-negative bacteria with high efficiency and they show structural similarities with longer insect- and mammal-derived antimicrobial
peptides. However, while the distant relatives appear to carry multiple functional domains, apidaecin, drosocin, formaecin
and pyrrhocoricin consist of only minimal determinants needed to penetrate across the cell membrane and bind to the target
biopolymer. These peptides appear to inhibit metabolic processes, such as protein synthesis or chaperone-assisted protein
folding. Pyrrhocoricin derivatives protect mice from experimental infections in vivo, suggesting the utility of modified analogs
in the clinical setting. Sequence variations of the target protein at the peptide-binding site may allow the development of
new peptide variants that kill currently unresponsive strains or species.
Received 12 December 2001; received after revision 11 February 2002; accepted 19 February 2002 相似文献
18.
Giuliani A Pirri G Bozzi A Di Giulio A Aschi M Rinaldi AC 《Cellular and molecular life sciences : CMLS》2008,65(16):2450-2460
The innate immunity of multicellular organisms relies in large part on the action of antimicrobial peptides (AMPs) to resist microbial invasion. Crafted by evolution into an extremely diversified array of sequences and folds, AMPs do share a common amphiphilic 3-D arrangement. This feature is directly linked with a common mechanism of action that predominantly (although not exclusively) develops upon interaction of peptides with cell membranes of target cells. This minireview reports on current understanding of the modes of interaction of AMPs with biological and model membranes, especially focusing on recent insights into the folding and oligomerization requirements of peptides to bind and insert into lipid membranes and exert their antibiotic effects. Given the potential of AMPs to be developed into a new class of anti-infective agents, emphasis is placed on how the information on peptide-membrane interactions could direct the design and selection of improved biomimetic synthetic peptides with antibiotic properties. 相似文献
19.
Pietersz GA Apostolopoulos V McKenzie IF 《Cellular and molecular life sciences : CMLS》2000,57(2):290-310
Tumor immunotherapy is currently receiving close scrutiny. However, with the identification of tumor antigens and their production by recombinant means, the use of cytokines and knowledge of major histocompatibility complex (MHC) class I and class II presentation has provided ample reagents for use and clear indications of how they should be used. At this time, much attention is focused on using peptides to be presented by MHC class I molecules to both induce and be targets for CD8+ cytolytic T cells. Many peptides generated endogenously or given exogenously can enter the class I pathway, but a number of other methods of entering this pathway are also known and are discussed in detail herein. While the review concentrates on inducing cytotoxic T cells (CTLs), it is becoming increasingly apparent that other modes of immunotherapy would be desirable, such as class II presentation to induce increased helper activity (for CTL), but also activating macrophages to be effective against tumor cells. 相似文献
20.
Endogenous opioids have been studied extensively since their discovery, in the hope of finding a perfect analgesic, devoid
of the secondary effects of alkaloid opioids. However, the design of selective opioid agonists has proved very difficult.
First, structural studies of peptides in general are hampered by their intrinsic flexibility. Second, the relationship between
constitution and the so-called 'bioactive conformation' is far from obvious. Ideally, a direct structural study of the complex
between a peptide and its receptor should answer both questions, but such a study is not possible, because opioid receptors
are large membrane proteins, difficult to study by standard structural techniques. Thus, conformational studies of opioid
peptides are still important for drug design and also for indirect receptor mapping. This review deals with conformational
studies of natural opioid peptides in several solvents that mimic in part the different environments in which the peptides
exert their action. None of the structural investigations yields a convincing bioactive conformation, but the global conformation
of longer peptides in biomimetic environments can shed light on the interaction with receptors.
Received 15 April 2001; received after revision 10 May 2001; accepted 11 May 2001 相似文献