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1.
Brandsch M 《Amino acids》2006,31(2):119-136
Summary. Membrane transport of L-proline has received considerable attention in basic and pharmaceutical research recently. Of the
most recently cloned members of the solute carrier family, two are “proline transporters”. The amino acid transporter PAT1,
expressed in intestine, kidney, brain and other organs, mediates the uptake of proline and derivatives in a pH gradient-dependent
manner. The Na+-dependent proline transporter SIT1, cloned in 2005, exhibits the properties of the long-sought classical IMINO system. Proline-containing
peptides are of interest for several reasons. Many biologically important peptide sequences contain highly conserved proline
residues. Xaa-Pro peptides are very often resistant to enzymatic hydrolysis and display, in contrast to Pro-Xaa peptides,
a high affinity to the H+/peptide cotransporter PEPT1 which is expressed in intestinal, renal, lung and biliary duct epithelial cells. Furthermore,
several orally available drugs are recognized by PEPT1 as Xaa-Pro analogues due to their sterical resemblance to small peptides. 相似文献
2.
Using string kernel to predict signal peptide cleavage site based on subsite coupling model 总被引:2,自引:0,他引:2
Summary. Owing to the importance of signal peptides for studying the molecular mechanisms of genetic diseases, reprogramming cells
for gene therapy, and finding new drugs for healing a specific defect, it is in great demand to develop a fast and accurate
method to identify the signal peptides. Introduction of the so-called {−3,−1, +1} coupling model (Chou, K. C.: Protein Engineering, 2001, 14–2, 75–79) has made it possible to take into account the coupling effect among some key subsites and hence can significantly
enhance the prediction quality of peptide cleavage site. Based on the subsite coupling model, a kind of string kernels for
protein sequence is introduced. Integrating the biologically relevant prior knowledge, the constructed string kernels can
thus be used by any kernel-based method. A Support vector machines (SVM) is thus built to predict the cleavage site of signal
peptides from the protein sequences. The current approach is compared with the classical weight matrix method. At small false
positive ratios, our method outperforms the classical weight matrix method, indicating the current approach may at least serve
as a powerful complemental tool to other existing methods for predicting the signal peptide cleavage site.
The software that generated the results reported in this paper is available upon requirement, and will appear at http://www.pami.sjtu.edu.cn/wm.
An erratum to this article is available at . 相似文献
3.
Summary. This mini-review presents the research carried out within the context of two of the main hypotheses of the aetiology of coeliac
disease. The enzymopathic hypothesis of the disease has been placed clearly as the underlying deficiency causing increased
levels of toxic peptides, while the immunological hypothesis has been implicated in the pathogenesis of the disorder as the
result of the action of undigested peptides in the small intestine.
As a consequence, we are proposing a unified hypothesis of coeliac disease, which takes into account the actions of these
undigested peptides through their direct cytotoxicity and their immunoactivity. At the same time, work aimed at defining some
of these biologically active peptides, which could be said to be involved in the aetiopathogenesis of coeliac disease, will
be reported.
The review also focusses on the use of enzyme therapy for management of the disease, which when used in conjunction with the
gluten-free diet, offers a safeguard against damage to the small intestine caused by small amounts of gluten. 相似文献
4.
Summary. It was the aim of this study to evaluate the potential of thiolated polycarbophil for the nasal administration of Leucine-enkephalin
(Leu-enkephalin). The enzymatic degradation of Leu-enkephalin on freshly excised bovine nasal mucosa was analysed qualitatively
via thin layer chromatography and quantitatively via high performance liquid chromatography (HPLC). The potential of thiolated
polycarbophil gels to provide a sustained release for the therapeutic peptide was investigated via diffusion studies. Permeation
studies were performed in Ussing-type diffusion chambers with freshly excised bovine nasal mucosa. Results demonstrated that
Leu-enkephalin is mainly degraded by the cleavage of tyrosine from the N-terminus of the peptide. Within one hour more than
63.5 ± 2% of this therapeutic peptide are degraded on the nasal mucosa. In the presence of 0.25% thiolated polycarbophil,
this degradation process, however, could be significantly lowered. Diffusion studies demonstrated that Leu-enkephalin being
incorporated in a 0.5% thiolated polycarbophil gel is sustained released out of it. The appearent permeability coefficient
(Papp) for Leu-enkephalin on the nasal mucosa was determined to be 1.9 ± 1.2 × 10−7 cm/sec. Furthermore, in the presence of 0.5% thiolated polycarbophil and 1% glutathione, which is used as permeation mediator
for the thiomer, the uptake of Leu-enkephalin from the nasal mucosa was even 82-fold improved. According to these results
thiolated polycarbophil might be a promising excipient for nasal administration of Leu-enkephalin. 相似文献
5.
Summary. To date, the majority of therapeutic peptides and proteins have to be administered via parenteral routes, which are painful
and inconvenient. In order to gain sufficient high blood concentrations after oral application, various barriers in the gastrointestinal
tract have to be overcome. Apart from a poor membrane uptake and intense enzymatic degradation, this study will demonstrate
that thiol–disulphide reactions are an underestimated essential part of the presystemic metabolism. Glutathione, integrative
part of the antioxidant defence system in the gastrointestinal tract, may play an important role in the inactivation of orally
given peptides and proteins. In order to verify this hypothesis, desmopressin which bears a single disulphide bond was used
as model peptide drug. Desmopressin was incubated with GSH in various concentrations, and the extent of thiol/disulphide exchange
reactions between the peptide drug and GSH was investigated in dependence on pH and ratio of reactants determined as a function
of time via HPLC, LC-MS and Maldi-Tof-MS analyses.
Results showed that desmopressin is degraded by 1% reduced glutathione at pH 4 and pH 5.5. In presence of 0.01%, 0.1% and
1% of reduced glutathione 6.1%, 19.4% and 52.1% of desmopressin, respectively, were degraded. The masses of the conjugates
after deconvolution measured by liquid chromatography and electrospray ionisation mass spectrometric detection were m/z 1069.67, m/z 1376.50, m/z 1683.40 and m/z 2138. These molecular masses, confirmed by Maldi-Tof-MS analysis, correspond with the masses of conjugates expected in theory.
Under defined conditions, these results reveal that thiol–disulphide exchange reactions have a considerable impact on the
alteration of peptide drugs and proteins. 相似文献
6.
Døskeland AP 《Amino acids》2006,30(1):99-103
Summary. A simple method is described to identify signature peptides derived from polyubiquitin (polyUb) chains. The method is based
on MALDI-TOF MS/MS analysis after chemically assisted fragmentation, and works on peptides isolated from polyacrylamide gels.
PolyUb chains branched at K48 and K63 were chosen as models for Ub-protein conjugates. They were resolved by SDS-PAGE, and
their tryptic peptides (in-gel-trypsinolysis) derivatized with 3-sulfopropinic acid NHSester to obtain chemically assisted
fragmentation during the MS/MS analysis. PolyUb-K63 produced a single peptide identified as 55TLSDYNIQK63 (GG)ESTLHLVLR72. PolyUb-K48 produced two branched signature peptides identified as 43LIFAGK48(GG)QLEDGR54 and 43LIFAGK48(LRGG)QLEDGR54. The recovery of signature peptide with LRGG as branched chain underscores the need to take limited proteolysis into account
in the search for detection of ubiquitinated peptides in proteomics studies. In conclusion, a simple method has been described
allowing the identification of signature peptides, which are diagnostic markers of the majority of polyUb-conjugated proteins.
In principle, the method should be applicable also for other more rare signature peptides. 相似文献
7.
Summary. Gliotransmission is a process in which astrocytes are dynamic elements that influence synaptic transmission and synaptogenesis.
The best-known gliotransmitters are glutamate and ATP. However, in the past decade, it has been demonstrated that D-serine,
a D-amino acid, acts as a gliotransmitter in glutamatergic synapses. The physiological relevance of D-serine is sustained
by the way in which it modulates the action of glutamatergic neurotransmission, neuronal migration and long-term potentiation
(LTP). In addition, the synthesis and degradation mechanisms of D-serine have been proposed as potential therapeutic targets
for the treatment of Alzheimer’s disease, schizophrenia and related disorders. In the present review, detailed information
is provided about the physiological and physiopathological relevance of D-serine, including metabolic and regulation aspects. 相似文献
8.
Summary. Involvement of individual antioxidant proteins (AOXP) and antioxidants in the differentiation process has been already reported.
A systematic search strategy for detecting differentially regulated AOXP in neuronal differentiation, however, has not been
published so far. The aim of this study was to provide an analytical tool identifying AOXP and to generate a differentiation-related
AOXP expressional pattern.
The undifferentiated N1E-115 neuroblastoma cell line was switched into a neuronal phenotype by DMSO treatment and used for
proteomic experiments: We used two-dimensional gel electrophoresis followed by unambiguous mass spectrometrical (MALDI-TOF-TOF)
identification of proteins to generate a map of AOXP.
16 AOXP were unambiguously determined in both cell lines; catalase, thioredoxin domain-containing protein 4 and hypothetical
glutaredoxin/glutathione S-transferase C terminus-containing protein were detectable in the undifferentiated cells only. Five
AOXP were observed in both, undifferentiated and differentiated cells and thioredoxin, thioredoxin-like protein p19, thioredoxin
reductase 1, superoxide dismutases (Mn and Cu-Zn), glutathione synthetase, glutathione S-transferase P1 and Mu1 were detected
in differentiated cells exclusively.
Herein a differential expressional pattern is presented that reveals so far unpublished antioxidant principles involved in
neuronal differentiation by a protein chemical approach, unambiguously identifying AOXP. This finding not only shows concomitant
determination of AOXP but also serves as an analytical tool and forms the basis for design of future studies addressing AOXP
and differentiation per se. 相似文献
9.
Harro J 《Amino acids》2006,31(3):215-230
Summary. Short CCK peptides elicit panic attacks in humans and anxiogenic-like effects in some animal models, but CCK receptor antagonists
have not been found clinically effective. Yet CCK overactivity appears to be involved in submissive behaviour, and CCKB receptor expression and binding are increased in suicide victims and animal models of anxiety. Preliminary data suggest that
involvement of CCK and its receptor subtypes in anxiety can be better described when focusing on distinct endophenotypes,
and considering environmental contingencies and confounds originating from interactions with dopamin-, opioid- and glutamatergic
neurotransmission. In contrast, NPY is an anti-anxiety peptide with robust effects in various animal models when administrated
into several brain regions. Studies with non-peptide antagonists selective for receptor subtypes have revealed the role of
endogenous NPY in active coping. At least Y1, Y2 and Y5 receptors in various brain regions are involved, with the strongest evidence for contribution of Y1. 相似文献
10.
Summary. The five regioisomeric bromotryptophans (BrTrps) play an important role in the life of sponges and lower marine invertebrates.
These bromo-amino acids, which are formed by post-translational modifications, are not found in nature in their free state,
but rather are involved in more complex structures. Any of the BrTrps can be part of a peptide, a cyclic peptide, an indole
alkaloid, an ergot alkaloid, a macrocycle and others. The present review covers the synthesis, physical and spectroscopic
properties of the five BrTrps. It also describes the many exiting pharmacological and biological activities played by the
BrTrps and by various secondary metabolites containing brominated tryptophan moieties. Of special interest are cyclic peptides
containing the 2-BrTrp unit, which were isolated from marine sponges e.g. konbamide, orbiculamide A, the various keramamides,
jaspamide eusynstyelamide and more. Important families of non-cyclic peptides containing the 6-BrTrp, include the styelins,
the conotoxins, the cathelicidins and several constrained macrocyclic peptides. Many marine secondary BrTrp-containing, non-peptidic
metabolites also display a remarkable spectrum of bioactivities, which can be harnessed for therapeutic and other purposes.
Examples are: barettin, bromotryptanthrin, tetraacetyl clionamide, cyclocinamide A, clavicipitic acid, various brominated
β-carbolines. In this review we have presented the various synthetic routes leading to the preparation of the five BrTrps
and many of its derivatives. Also, we have introduced the reader to many synthetic routes leading to BrTrp-containing non-peptidic
natural products. Although the functional role of the various compounds in the human body is only poorly understood, its effects
were extensively studied. Almost all of these compounds exhibit important therapeutic properties e.g. antifungal, antimicrobial,
antihelmintic, insecticidal ichthyotoxic and anticancer activity. In the present review attempts have been made to provide
synopsis, synthesis and symbiosis of chemical and biological actions, which may provide future guidance and facilitate further
research in this area. 相似文献
11.
Predicting secretory protein signal sequence cleavage sites by fusing the marks of global alignments
Summary. A newly synthesized secretory protein in cells bears a special sequence, called signal peptide or sequence, which plays the
role of “address tag” in guiding the protein to wherever it is needed. Such a unique function of signal sequences has stimulated
novel strategies for drug design or reprogramming cells for gene therapy. To realize these new ideas and plans, however, it
is important to develop an automated method for fast and accurately identifying the signal sequences or their cleavage sites.
In this paper, a new method is developed for predicting the signal sequence of a query secretory protein by fusing the results
from a series of global alignments through a voting system. The very high success rates thus obtained suggest that the novel
approach is very promising, and that the new method may become a useful vehicle in identifying signal sequence, or at least
serve as a complementary tool to the existing algorithms of this field. 相似文献
12.
Functional roles of microglia in the central nervous system 总被引:2,自引:0,他引:2
Microglia, a type of perineuronal glial cells in the central nervous system, have been suggested to play various important roles in normal and pathologic brains. In this article, first, we described the association or roles of activated microglia in injury and various brain diseases, and subsequently, summarized microglia-derived physiologically active molecules which will affect the neuronal survival and neuronal growth, and glial function, and finally, discussed the molecular mechanism of microglial activation. 相似文献
13.
Peptaibiomics: an advanced, rapid and selective analysis of peptaibiotics/peptaibols by SPE/LC-ES-MS
Summary. “Proteomics” and “peptidomics” are used as technical terms to define the analysis and study of all proteins and peptides expressed
in an organism or tissue. In analogy we propose the name peptaibiomics for the analysis of a group of fungal peptide antibiotics (peptaibiotics) containing the characteristic amino acid Aib (α-aminoisobutyric
acid). In analogy to the peptidome the complete expression of peptaibiotics by fungal multienzyme complexes should be named
the peptaibiome.
Peptaibiotics are defined as peptides containing Aib and exerting a variety of bioactivities. They comprise the sub-groups
of N-acetylated peptaibols, characterized also by a C-terminal amide-linked 2-amino alcohol, and lipopeptaibols having in place of an acetyl group a lipophilic fatty acid acyl
group. Furthermore, lipoaminopeptides are also known with long-chain fatty acid on the N-termini, a lipoamino acid in position three and a strongly basic secondary or tertiary amine form a subgroup of mixed forms
which could not be integrated in one of these three previously mentioned groups.
Here we present a specific and rapid screening method on the peptaibiome applicable directly onto filamentous fungi cultured
in a single Petri dish. The method comprises solid-phase extraction (SPE) of peptaibiotics followed by on-line reversed-phase
HPLC coupled to an ion trap electrospray tandem mass spectrometer (ES-MS). The presence of these peptides is indicated by
characteristic mass differences of Δm = 85.1 Da representing Aib-residues which can be observed in the b-series of acylium fragment ions resulting from ES-MS. Partial sequences can be deduced from the data and compared with structures
compiled in electronic peptaibol data bases. The judgement is possible whether or not structures are novel, already known
or related to known structures. Suitability of the method is demonstrated with the analysis of strains of Trichoderma and its teleomorph Hypocrea. New sequences of peptaibiotics are presented and those being related to established 10- to 18-residue peptaibols trichovirin,
trichogin and trichotoxin, which have been described in the literature. 相似文献
14.
Axelsen LN Haugan K Stahlhut M Kjølbye AL Hennan JK Holstein-Rathlou NH Petersen JS Nielsen MS 《The Journal of membrane biology》2007,216(1):23-35
Much of our current knowledge about the physiological and pathophysiological role of gap junctions is based on experiments
where coupling has been reduced by either chemical agents or genetic modification. This has brought evidence that gap junctions
are important in many physiological processes. In a number of cases, gap junctions have been implicated in the initiation
and progress of disease, and experimental uncoupling has been used to investigate the exact role of coupling. The inverse
approach, i.e., to increase coupling, has become possible in recent years and represents a new way of testing the role of
gap junctions. The aim of this review is to summarize the current knowledge obtained with agents that selectively increase
gap junctional intercellular coupling. Two approaches will be reviewed: increasing coupling by the use of antiarrhythmic peptide
and its synthetic analogs and by interfering with the gating of gap junctional channels. 相似文献
15.
Summary. The condensation reactions of sodium trimetaphosphate with single amino acids, namely glycine, L-alanine, β-alanine and γ-aminobutyric
acid or pairs of these amino acids were reinvestigated by electrospray ion-trap mass spectrometry and high performance liquid
chromatography. It was found when mixtures were treated by sodium trimetaphosphate only in the presence of α-amino acid dipeptides
were formed. Without addition of α-amino acids, the β-amino acid or γ-aminobutyric acid could not form peptide either by themselves
or with their mixtures under the same conditions. From the data it is concluded that phosphate might select α-amino acids
to produce the peptides being important precursors for the origin of life.
Authors’ address: Dr. Pengxiang Xu, The Key Laboratory for Chemical Biology of Fujian Province, Department of Chemistry, Xiamen
University, Xiamen 361005, China 相似文献
16.
17.
Summary. In this investigation, we attempted to study the backbone geometry of amino acids in peptides using C′ deviation. Diameters
of distribution were used to describe the various atomic structures, and scatter graphs provided visual evaluation. The length
of peptide fragments and the secondary structure of amino acids in the central position of the peptide fragments were also
analyzed. The results showed that the atomic distribution of the central amino acids of five-residue peptide fragments was
much more restricted than that of their corresponding three-residue peptide fragments. In identical three-residue fragments,
atoms of central amino acids with different secondary structures, were distributed in distinct areas. 相似文献
18.
Arriagada C Dagnino-Subiabre A Caviedes P Armero JM Caviedes R Segura-Aguilar J 《Amino acids》2000,18(4):363-373
Summary. Aminochrome was found to be toxic in a mouse-derived neuronal cell line (CNh). The effect was concentration dependent (10–150
μM). The issue whether aminochrome toxicity involves glutamate transmission was studied with several glutamate receptors antagonists.
Incubation of the cells with aminochrome (150 μM) in the presence of 100 μM of the AMPA an-tagonist, NBQX resulted in an increase of cell survival, from 52 to 73%. However, this protective effect
did not seem to be related to activation of ionotropic glutamate receptors since incubation of CNh cells with 200 μM of glutamate resulted in only 10% decrease of cell survival. However, NBQX was found to inhibit in vitro the autoxidation process. One hundred μM AP-5 did not have any effect on aminochrome toxicity. The toxic effect of aminochrome on CNh cells seems to be dependent
of extracellular activation since addition of dicoumarol, a specific inhibitor of DT-diaphorase, did not affect that toxicity,
which can be explained perhaps by a lack of a transport system for aminochrome into the CNh cells.
Received July 28, 1999, Accepted December 6, 1999 相似文献
19.
Summary. In this paper, the analog of arginine residues in peptides was synthesized and characterized by ESI-MS/MS (electrospray ionization
with tandem mass spectrometry), 31P NMR, 1H NMR, IR and high-resolution mass spectrometry. When the Todd reaction activity of the guanidino group in free arginine and
the arginine peptide analog were compared, it was found that the proton affinity of the guanidino group was decreased when
both the N- and the C-terminal were blocked. As a result, the guanidino group of arginine residues in peptides could be phosphorylated
under the Todd reaction condition, but not the free arginine. This result was further proved by the theoretical calculation
of their proton affinity. 相似文献
20.
Tomato (Lycopersicon esculentum Mill.) prosystemin in fusion with a viral signal peptide was expressed in Sf21 insect cell cultures after infection with recombinant baculoviruses. Prosystemin was purified from culture supernatants
and its identity was confirmed by N-terminal sequence and mass-spectral analyses. Recombinant prosystemin was found to be
equally active as compared to systemin in inducing the expression of wound-response genes in tomato plants. In cultured cells
of L. peruvianum, prosystemin elicited a rapid alkalinization of the growth medium. The timing and dose-dependence of the alkalinization response
were found to be identical for prosystemin and systemin, respectively. Prosystemin-triggered defense responses were inhibited
by a competitive antagonist of systemin activity, indicating that the systemin sequence within the primary structure of prosystemin
determines its activity.
Received: 30 August 1999 / Accepted: 6 December 1999 相似文献