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1.
Toniolo C Crisma M Formaggio F Peggion C Epand RF Epand RM 《Cellular and molecular life sciences : CMLS》2001,58(9):1179-1188
Lipopeptaibols are members of a novel group of naturally occurring, short peptides with antimicrobial activity, characterized
by a lipophilic acyl chain at the N-terminus, a high content of the turn/helix forming α-aminoisobutyric acid and a 1,2-amino alcohol at the C-terminus. The amino acid sequences range from 6 to 10 residues and
the fatty acyl moieties from 8 to 15 carbon atoms. The peptide portion of lipopeptaibols can be shorter than those of the
nonlipidated peptaibols that range from 10 to 19 amino acid residues. The longest peptides fold into a mixed 310/α helix, whereas the shortest peptides tend to adopt a β-turn/sheet structure. Using solution methodologies, a series of analogues of trichogin GA IV was synthesized which allowed
determination of the minimal lipid chain and peptide main-chain lengths for the onset of membrane activity and exploitation
of a number of spectroscopic techniques aimed at determining its preferred conformation under a variety of conditions and
investigating in detail its mode of interaction with, and its effect on, the phospholipid membranes.
Received 26 January 2001; received after revision 7 March 2001; accepted 15 March 2001 相似文献
2.
Penaeidins, a family of antimicrobial peptides from penaeid shrimp (Crustacea, Decapoda) 总被引:13,自引:0,他引:13
Destoumieux D Munoz M Bulet P Bachère E 《Cellular and molecular life sciences : CMLS》2000,57(8-9):1260-1271
The production of antimicrobial peptides represents a first-line host defense mechanism of innate immunity that is widespread
in nature. Only recently such effectors were isolated in crustacean species, whereas numerous antimicrobial peptides have
been characterized from other arthropods, both insects and chelicerates. This review presents findings on a family of antimicrobial
peptides, named penaeidins, isolated from the shrimp Penaeus vannamei. Their structure and antimicrobial properties as well as their immune function will be discussed through analyses of penaeidin
gene expression and peptide distribution upon microbial challenge.
Received 21 January 2000; received after revision 10 March 2000; accepted 10 March 2000 相似文献
3.
Carballar-Lejarazú R Rodríguez MH de la Cruz Hernández-Hernández F Ramos-Castañeda J Possani LD Zurita-Ortega M Reynaud-Garza E Hernández-Rivas R Loukeris T Lycett G Lanz-Mendoza H 《Cellular and molecular life sciences : CMLS》2008,65(19):3081-3092
Scorpine is an antimicrobial peptide whose structure resembles a hybrid between a defensin and a cecropin. It exhibits antibacterial
activity and inhibits the sporogonic development of parasites responsible for murine malaria. In this communication we report
the production of scorpine in a heterelogous system, using a specific vector containing its cloned gene. The recombinantly
expressed scorpine (RScp) in Anopheles gambie cells showed antibacterial activity against Bacillus subtilis and Klebsiella pneumoniae, at 5 and 10 μM, respectively. It also produced 98% mortality in sexual stages of Plasmodium berghei at 15 μM and 100% reduction in Plasmodium falciparum parasitemia at 5 μM. RScp also inhibited virus dengue-2 replication in C6/36 mosquito cells. In addition, we generated viable
and fertile transgenic Drosophila that overexpresses and correctly secretes RScp into the insect hemolymph, suggesting that the generation of transgenic mosquitoes
resistant to different pathogens may be viable.
Received 6 May 2008; received after revision 24 July 2008; accepted 29 July 2008 相似文献
4.
Proline-rich antimicrobial peptides are a group of cationic host defense peptides of vertebrates and invertebrates characterized
by a high content of proline residues, often associated with arginine residues in repeated motifs. Those isolated from some
mammalian and insect species, although not evolutionarily related, use a similar mechanism to selectively kill Gram-negative
bacteria, with a low toxicity to animals. Unlike other types of antimicrobial peptides, their mode of action does not involve
the lysis of bacterial membranes but entails penetration into susceptible cells, where they then act intracellularly. Some
aspects of the transport system and cytoplasmic targets have been elucidated. These features make them attractive both as
anti-infective lead compounds and as a new class of potential cell-penetrating peptides capable of internalising membrane-impermeant
drugs into both bacterial and eukaryotic cells 相似文献
5.
Naturally occurring antimicrobial peptides (AMPs) present several drawbacks that strongly limit their development into therapeutically
valuable antibiotics. These include susceptibility to protease degradation and high costs of manufacture. To overcome these
problems, researchers have tried to develop mimics or peptidomimetics endowed with better properties, while retaining the
basic features of membrane-active natural AMPs such as cationic charge and amphipathic design. Protein epitope mimetics, multimeric
(dendrimeric) peptides, oligoacyllysines, ceragenins, synthetic lipidated peptides, peptoids and other foldamers are some
of the routes explored so far. The synthetic approach has led to compounds that have already entered clinical evaluation for
the treatment of specific conditions, such as Staphylococcus (MRSA) infections. Should these trials be successful, an important proof-of-concept would be established, showing that synthetic
oligomers rather than naturally occurring molecules could bring peptide-based antibiotics to clinical practice and the drug
market for local and systemic treatment of medical conditions associated with multi-drug resistant pathogens. 相似文献
6.
Epithelial antimicrobial peptides: innate local host response elements 总被引:23,自引:0,他引:23
Schröder JM 《Cellular and molecular life sciences : CMLS》1999,56(1-2):32-46
Multicellular organisms have to survive in an environment laden with numerous microorganisms, which represent a potential hazard to life. Different strategies have been developed to ward off infections by preventing microorganisms from entering surfaces and by preventing the attack of microorganisms that have already entered the epithelia. Therefore, it is not surprising that epithelia are equipped with various antimicrobial substances that act rapidly to kill a broad range of microorganisms. This review summarizes our present knowledge about epithelial peptide antibiotics produced in plants, invertebrates, and vertebrates including humans. There is now strong evidence that in addition to constitutively secreted peptide antibiotics, others are induced upon contact with microorganisms or by proinflammatory cytokines. beta-Defensins represent one family of vertebrate antimicrobial peptides, members of which are inducible and have recently been identified in humans. The defensin-characteristic local expression pattern may indicate that specialized surfaces express a characteristic surface antimicrobial peptide pattern that might define the characteristic microflora as well as the density of microorganisms present on the surface. 相似文献
7.
8.
Tommy Baumann Urs Kämpfer Stefan Schürch Johann Schaller Carlo Largiadèr Wolfgang Nentwig Lucia Kuhn-Nentwig 《Cellular and molecular life sciences : CMLS》2010,67(16):2787-2798
Three novel glycine-rich peptides, named ctenidin 1–3, with activity against the Gram-negative bacterium E. coli, were isolated and characterized from hemocytes of the spider Cupiennius salei. Ctenidins have a high glycine content (>70%), similarly to other glycine-rich peptides, the acanthoscurrins, from another spider, Acanthoscurria gomesiana. A combination of mass spectrometry, Edman degradation, and cDNA cloning revealed the presence of three isoforms of ctenidin, at least two of them originating from simple, intronless genes. The full-length sequences of the ctenidins consist of a 19 amino acid residues signal peptide followed by the mature peptides of 109, 119, or 120 amino acid residues. The mature peptides are post-translationally modified by the cleavage of one or two C-terminal cationic amino acid residue(s) and amidation of the newly created mature C-terminus. Tissue expression analysis revealed that ctenidins are constitutively expressed in hemocytes and to a small extent also in the subesophageal nerve mass. 相似文献
9.
Zhu S 《Cellular and molecular life sciences : CMLS》2008,65(7-8):1285-1294
The cathelin-like domain (CLD) of cathelicidins is grouped in the same superfamily with cystatins, natural cysteine protease
inhibitors, due to their structural similarity. Intriguingly, human hCAP-18/LL37 and pig protegrin-3 (PG3) CLDs exhibit opposite
effects against cathepsin L. Here, I evaluated the functional importance of the CLD through identifying whether positive selection
has driven adaptive evolution of this domain. As a result, four positively selected sites were detected and three of them
are located on a loop region previously recognized as a key determinant of the activating effect of the PG3 CLD. Analysis
of amino acid variability of the CLD led to the discovery of a conserved region and three highly variable regions, in which
two are subjected to positive selection. Positive selection targeting the variable regions provides a starting point for experimentally
establishing a direct link between the observed amino acid changes and functional divergence of the CLD family.
Received 8 February 2008; accepted 13 February 2008 相似文献
10.
Antimicrobial agents are toxic to bacteria by a variety of mechanisms. One mechanism that is very dependent on the lipid composition of the bacterial membrane is the clustering of anionic lipid by cationic antimicrobial agents. Certain species of oligo-acyl-lysine (OAK) antimicrobial agents are particularly effective in clustering anionic lipids in mixtures mimicking the composition of bacterial membranes. The clustering of anionic lipids by certain cationic antimicrobial agents contributes to the anti-bacterial action of these agents. Bacterial membrane lipids are a determining factor, resulting in some species of bacteria being more susceptible than others. In addition, lipids can be used to increase the effectiveness of antimicrobial agents when administered in vivo. Therefore, we review some of the structures in which lipid mixtures can assemble, to more effectively be utilized as antimicrobial delivery systems. We describe in more detail the complexes formed between mixtures of lipids mimicking bacterial membranes and an OAK and their usefulness in synergizing with antibiotics to overcome bacterial multidrug resistance. 相似文献
11.
Myelin basic protein: a multifunctional protein 总被引:1,自引:1,他引:0
Boggs JM 《Cellular and molecular life sciences : CMLS》2006,63(17):1945-1961
Myelin basic protein (MBP), the second most abundant protein in central nervous system myelin, is responsible for adhesion
of the cytosolic surfaces of multilayered compact myelin. A member of the ‘intrinsically disordered’ or conformationally adaptable
protein family, it also appears to have several other functions. It can interact with a number of polyanionic proteins including
actin, tubulin, Ca2+-calmodulin, and clathrin, and negatively charged lipids, and acquires structure on binding to them. It may act as a membrane
actin-binding protein, which might allow it to participate in transmission of extracellular signals to the cytoskeleton in
oligodendrocytes and tight junctions in myelin. Some size isoforms of MBP are transported into the nucleus and thus they may
also bind polynucleotides. Extracellular signals received by myelin or cultured oligodendrocytes cause changes in phosphorylation
of MBP, suggesting that MBP is also involved in signaling. Further study of this very abundant protein will reveal how it
is utilized by the oligodendrocyte and myelin for different purposes.
Received 2 March 2006; received after revision 12 April 2006; accepted 16 May 2006 相似文献
12.
Amy A. Baxter Fung T. Lay Ivan K. H. Poon Marc Kvansakul Mark D. Hulett 《Cellular and molecular life sciences : CMLS》2017,74(20):3809-3825
There is an ongoing need for effective and targeted cancer treatments that can overcome the detrimental side effects presented by current treatment options. One class of novel anticancer molecules with therapeutic potential currently under investigation are cationic antimicrobial peptides (CAPs). CAPs are small innate immunity peptides found ubiquitously throughout nature that are typically membrane-active against a wide range of pathogenic microbes. A number of CAPs can also target mammalian cells and often display selective activity towards tumor cells, making them attractive candidates as novel anticancer agents warranting further investigation. This current and comprehensive review describes key examples of naturally occurring membrane-targeting CAPs and their modified derivatives that have demonstrated anticancer activity, across multiple species of origin and structural subfamilies. In addition, we address recent advances made in the field and the ongoing challenges faced in translating experimental findings into clinically relevant treatments. 相似文献
13.
The role of mammalian antimicrobial peptides and proteins in awakening of innate host defenses and adaptive immunity 总被引:33,自引:1,他引:32
Since we live in a dirty environment, we have developed many host defenses to contend with microorganisms. The epithelial lining of our skin, gastrointestinal tract and bronchial tree produces a number of antibacterial peptides, and our phagocytic neutrophils rapidly ingest and enzymatically degrade invading organisms, as well as produce peptides and enzymes with antimicrobial activities. Some of these antimicrobial moieties also appear to alert host cells involved in both innate host defense and adaptive immune responses. The epithelial cells are a source of constitutively produced beta defensin (HBD1) and proinflammatory cytokine-inducible beta defensins (HBD2 and -3) and cathelicidin (LL37). The neutrophils-derived antimicrobial peptides are released on demand from their cytoplasmic granules. They include the enzymes cathepsin G and chymase, azurocidin, a defensins and cathelicidin. In contrast, C5a and C3b are produced by activation of the serum complement cascade. The antimicrobial moieties direct the migration and activate target cells by interacting with selected G-protein-coupled seven-transmembrane receptors (GPCRs) on cell surfaces. The beta defensins interact with the CCR6 chemokine GPCRs, whereas cathelicidins interact with the low-affinity FPRL-1 receptors. The neutrophil-derived cathepsin G acts on the high-affinity FMLP receptor (GPCR) known as FPR, while the receptors for chymase and azurocidin have not been identified as yet. The serum-derived C5a uses a GPCR known as C5aR to mediate its chemotactic and cell-activating effects. Consequently, all these ligand-receptor interactions in addition to mediating chemotaxis also activate receptor-expressing cells to produce other mediators of inflammation. 相似文献
14.
Bocchinfuso G Bobone S Mazzuca C Palleschi A Stella L 《Cellular and molecular life sciences : CMLS》2011,68(13):2281-2301
Since their initial discovery, 30 years ago, antimicrobial peptides (AMPs) have been intensely investigated as a possible
solution to the increasing problem of drug-resistant bacteria. The interaction of antimicrobial peptides with the cellular
membrane of bacteria is the key step of their mechanism of action. Fluorescence spectroscopy can provide several structural
details on peptide–membrane systems, such as partition free energy, aggregation state, peptide position and orientation in
the bilayer, and the effects of the peptides on the membrane order. However, these “low-resolution” structural data are hardly
sufficient to define the structural requirements for the pore formation process. Molecular dynamics simulations, on the other
hand, provide atomic-level information on the structure and dynamics of the peptide–membrane system, but they need to be validated
experimentally. In this review we summarize the information that can be obtained by both approaches, highlighting their versatility
and complementarity, suggesting that their synergistic application could lead to a new level of insight into the mechanism
of membrane destabilization by AMPs. 相似文献
15.
Tsatsanis C Dermitzaki E Venihaki M Chatzaki E Minas V Gravanis A Margioris AN 《Cellular and molecular life sciences : CMLS》2007,64(13):1638-1655
Corticotropin-releasing factor (CRF), also termed corticotropin-releasing hormone (CRH) or corticoliberin, is the major regulator
of the adaptive response to internal or external stresses. An essential component of the adaptation mechanism is the adrenal
gland. CRF regulates adrenal function indirectly through the central nervous system (CNS) via the hypothalamic-pituitary-adrenal
(HPA) axis and via the autonomic nervous system by way of locus coeruleus (LC) in the brain stem. Accumulating evidence suggests
that CRF and its related peptides also affect the adrenals directly, i.e. not through the CNS but from within the adrenal gland where they form paracrine regulatory loops. Indeed, CRF and its related
peptides, the urocortins (UCNs: UCN1, UCN2 and UCN3), their receptors CRF type 1 (CRF1) and 2 (CRF2) as well as the endogenous pseudo-receptor CRF-binding protein (CRF-BP) are all expressed in adrenal cortical, medullary
chromaffin and resident immune cells. The intra-adrenal CRF-based regulatory system is complex and depends on the balance
between the local concentration of CRF ligands and the availability of their receptors.
Received 19 December 2006; received after revision 20 February 2007; accepted 26 March 2007 相似文献
16.
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
17.
Human seminal plasma spontaneously coagulates after ejaculation. The major component of this coagulum is semenogelin I, a
52-kDa protein expressed exclusively in the seminal vesicles. Recently, a sperm motility inhibitor has been found to be identical
to semenogelin I, suggesting that it may also be a physiological sperm motility inhibitor. The protein is rapidly cleaved
after ejaculation by the chymotrypsin-like prostatic protease prostate-specific antigen, resulting in liquefaction of the
semen coagulum and the progressive release of motile spermatozoa. Some of the cleavage products of Sg I may also have various
biological functions. While the semenogelin I protein is unique to human and higher primates, it has recently been shown to
belong to a gene family having a similar gene structure but encoding widely differing proteins. The recently elucidated characteristics
of the semenogelin I gene as well as the biochemical and functional properties of the encoded protein are reviewed, and an
attempt is made to integrate the various findings into a model for semen coagulation, sperm immobilization and potential other
functions.
Received 21 October 1998; received after revision 15 December 1998; accepted 15 December 1998 相似文献
18.
19.
R. Igic H. S. J. Yeh K. Sorrells E. G. Erdös 《Cellular and molecular life sciences : CMLS》1972,28(2):135-136
Zusammenfassung Ein Enzym (Angiotensin I «converting enzyme» oder Kininase II; DH) wurde aus Schweinelungen isoliert und gereinigt. DH splatet Dipeptide vom Carboxyterminus der Peptidsubstrate mit Einschluss von Bradykinin, Angiotensin I, B-Kette von Insulin und14C-DNS-Gly-Gly-Gly. Zu den besten Inhibitoren des Enzyms gehören zwei kürzlich synthetisierte Peptide sowie Glutathion und Insulin. Die Experimente deuten auf ein einziges Enzym hin, das alle erwähnten Substrate hydrolysiert.
Supported in part by grants No. HE 08764 and No. 5T01 HE 05859 from N.I.H., U.S.P.H.S. and by the O.N.R. No. N00014-68-A-0496 and No. N00014-69-A-0385.
During the tenure of a fellowship of the Oklahoma Heart Association.
Acknowledgements. MissDeborah Downs assisted us in some of the experiments. HHL was donated by Dr.D. Cushman of the Squibb Institute. 相似文献
Supported in part by grants No. HE 08764 and No. 5T01 HE 05859 from N.I.H., U.S.P.H.S. and by the O.N.R. No. N00014-68-A-0496 and No. N00014-69-A-0385.
During the tenure of a fellowship of the Oklahoma Heart Association.
Acknowledgements. MissDeborah Downs assisted us in some of the experiments. HHL was donated by Dr.D. Cushman of the Squibb Institute. 相似文献
20.
Pyridoxamine as a multifunctional pharmaceutical: targeting pathogenic glycation and oxidative damage 总被引:3,自引:0,他引:3
The discovery that pyridoxamine (PM) can inhibit glycation reactions and the formation of advanced glycation end products (AGEs) stimulated new interest in this B6 vitamer as a prospective pharmacological agent for treatment of complications of diabetes. The mechanism of action of PM includes: (i) inhibition of AGE formation by blocking oxidative degradation of the Amadori intermediate of the Maillard reaction; (ii) scavenging of toxic carbonyl products of glucose and lipid degradation; and (iii) trapping of reactive oxygen species. The combination of these multiple activities along with PM safety posture it as a promising drug candidate for treatment of diabetic complications as well as other multifactorial chronic conditions in which oxidative reactions and carbonyl compounds confer pathogenicity.Received 1 March 2005; received after revision 25 March 2005; accepted 31 March 2005 相似文献