共查询到20条相似文献,搜索用时 0 毫秒
1.
A. V. Chudinov V. D. Rumyantseva A. V. Lobanov G. K. Chudinova A. A. Stomakhin A. F. Mironov 《Russian Journal of Bioorganic Chemistry》2004,30(1):89-93
The ytterbium complex of 5,10,15,20-tetrakis(4-carboxyphenyl)porphyrin was synthesized as an IR-fluorescent label and covalently bound to bovine serum albumin. The resulting conjugate fluoresces at 985 nm and is of interest for use in IR-fluorescent tumor diagnostic, immunoassay, and energy transfer studies. 相似文献
2.
Miroshnichenko S. K. Amirloo B. Bichenkova E. V. Vlassov V. V. Zenkova M. A. Patutina O. A. 《Russian Journal of Bioorganic Chemistry》2019,45(6):803-812
Russian Journal of Bioorganic Chemistry - Nowadays, application of miRNases—artificial ribonucleases aimed at degradation of noncoding RNAs, in particular, miRNAs—represents one of the... 相似文献
3.
4.
Shane A. Liddelow Katarzyna M. Dzi?gielewska Kjeld M?llg?rd Sophie C. Whish Natassya M. Noor Benjamin J. Wheaton Renate Gehwolf Andrea Wagner Andreas Traweger Hannelore Bauer Hans-Christian Bauer Norman R. Saunders 《PloS one》2014,9(9)
To maintain the precise internal milieu of the mammalian central nervous system, well-controlled transfer of molecules from periphery into brain is required. Recently the soluble and cell-surface albumin-binding glycoprotein SPARC (secreted protein acidic and rich in cysteine) has been implicated in albumin transport into developing brain, however the exact mechanism remains unknown. We postulate that SPARC is a docking site for albumin, mediating its uptake and transfer by choroid plexus epithelial cells from blood into cerebrospinal fluid (CSF). We used in vivo physiological measurements of transfer of endogenous (mouse) and exogenous (human) albumins, in situ Proximity Ligation Assay (in situ PLA), and qRT-PCR experiments to examine the cellular mechanism mediating protein transfer across the blood–CSF interface. We report that at all developmental stages mouse albumin and SPARC gave positive signals with in situ PLAs in plasma, CSF and within individual plexus cells suggesting a possible molecular interaction. In contrast, in situ PLA experiments in brain sections from mice injected with human albumin showed positive signals for human albumin in the vascular compartment that were only rarely identifiable within choroid plexus cells and only at older ages. Concentrations of both endogenous mouse albumin and exogenous (intraperitoneally injected) human albumin were estimated in plasma and CSF and expressed as CSF/plasma concentration ratios. Human albumin was not transferred through the mouse blood–CSF barrier to the same extent as endogenous mouse albumin, confirming results from in situ PLA. During postnatal development Sparc gene expression was higher in early postnatal ages than in the adult and changed in response to altered levels of albumin in blood plasma in a differential and developmentally regulated manner. Here we propose a possible cellular route and mechanism by which albumin is transferred from blood into CSF across a sub-population of specialised choroid plexus epithelial cells. 相似文献
5.
Moataz Dowaidar Jakob Regberg Dimitar A. Dobchev Tõnis Lehto Mattias Hällbrink Mati Karelson Ülo Langel 《International journal of peptide research and therapeutics》2017,23(1):91-100
Cell-penetrating peptide (CPP) based transfection systems (PBTS) are a promising class of drug delivery vectors. CPPs are short mainly cationic peptides capable of delivering cell non-permeant cargo to the interior of the cell. Some CPPs have the ability to form non-covalent complexes with oligonucleotides for gene therapy applications. In this study, we use quantitative structure–activity relationships (QSAR) , a statistical method based on regression data analysis. Here, an fragment QSAR (FQSAR) model is developed to predict new peptides based on standard alpha helical conformers and Assisted Model Building with Energy Refinement molecular mechanics simulations of previous peptides. These new peptides were examined for plasmid transfection efficiency and compared with their predicted biological activity. The best predicted peptides were capable of achieving plasmid transfection with significant improvement compared to the previous generation of peptides. Our results demonstrate that FQSAR model refinement is an efficient method for optimizing PBTS for improved biological activity. 相似文献
6.
7.
David Barras Nadja Chevalier Vincent Zoete Rosemary Dempsey Karine Lapouge Monilola A. Olayioye Olivier Michielin Christian Widmann 《The Journal of biological chemistry》2014,289(34):23701-23711
TAT-RasGAP317–326, a cell-permeable 10-amino acid-long peptide derived from the N2 fragment of p120 Ras GTPase-activating protein (RasGAP), sensitizes tumor cells to apoptosis induced by various anticancer therapies. This RasGAP-derived peptide, by targeting the deleted in liver cancer-1 (DLC1) tumor suppressor, also hampers cell migration and invasion by promoting cell adherence and by inhibiting cell movement. Here, we systematically investigated the role of each amino acid within the RasGAP317–326 sequence for the anticancer activities of TAT-RasGAP317–326. We report here that the first three amino acids of this sequence, tryptophan, methionine, and tryptophan (WMW), are necessary and sufficient to sensitize cancer cells to cisplatin-induced apoptosis and to reduce cell migration. The WMW motif was found to be critical for the binding of fragment N2 to DLC1. These results define the interaction mode between the active anticancer sequence of RasGAP and DLC1. This knowledge will facilitate the design of small molecules bearing the tumor-sensitizing and antimetastatic activities of TAT-RasGAP317–326. 相似文献
8.
Amyloid β peptides appear to play a role in physiological processes; however, they are also involved in the pathogenesis of
Alzheimer disease. Their actions under normal conditions are probably mediated by soluble monomeric l-isoforms at low concentrations, perhaps via highly specific interactions. On the contrary, toxic effects of aggregated natural
l-isoforms/synthetic d-isoforms on membranes are very similar, but synthetic reverse/random l-isoforms without pronounced aggregation properties are not toxic. Our previous work reported interactions of non-aggregated/aggregated
l-isoforms of amyloid β peptides 1–40/1–42 with racemic 24-hydroxycholesterol. In this study, stereospecificity in the interactions
of natural 24(S)hydroxycholesterol (cerebrosterol) or synthetic 24(R)hydroxycholesterol with soluble fragment 1–40 was evaluated
by means of an in vitro test based on increased vulnerability of the hemicholinium-3 sensitive high-affinity choline uptake
system in rat hippocampal cholesterol-depleted synaptosomes to the actions of amyloid β; computational simulations were also
performed. Our results suggest that: (1) 24(S)hydroxycholesterol interacts with l-peptide 1–40 but not with the reverse l-peptide 40–1, (2) 24(R)hydroxycholesterol does not interact with l-peptide 1–40 or reverse 40–1, and (3) both enantiomers can probably interact with d-peptide 1–40. Therefore, the binding of 24(S)hydroxycholesterol is not fully stereospecific and the interaction could not
reflect a physiological mechanism. Data from the computational simulation indicate that the hydrophobic core of the amyloid
β molecule interacts with the hydrophobic part of 24(S)hydroxycholesterol, but no hydrogen bonds with high stability were
found. Using this procedure, globular amyloid β could retain 24(S)hydroxycholesterol and thus contribute to its pathological
accumulation in the brains of patients with Alzheimer disease. 相似文献
9.
Kazuki Sato Tadakazu Maeda Minako Hoshi 《International journal of peptide research and therapeutics》2012,18(4):341-345
In contrast to the general tendency of hydrophobicity-toxicity relationship of amyloid ?? peptide, we have previously found that the replacement of Asn27 of amyloid ??(25?C35) peptide with Ala yielded a more hydrophobic but less toxic analog and that of Met35 gave a less hydrophobic but more toxic one. To reveal the unique role of these two residues in the neurotoxicity of amyloid ??(1?C42) peptide, the major peptide constituent of amyloid plaques in human brain, we synthesized two analogs N27A and M35A in which Asn27 and Met35 of amyloid ??(1?C42) peptide was replaced with Ala, respectively. The former showed much weaker toxicity than the native peptide, while the latter showed almost an equivalent toxicity, indicating that the side chain amide group of Asn27 has an essential role for the toxicity of amyloid ?? peptides. 相似文献
10.
Henning Urlaub Bernd Thiede Eva-Christina Müller Brigitte Wittmann-Liebold 《The protein journal》1997,16(5):375-383
We have investigated peptide–oligoribonucleotide complexes isolated from cross-linked Escherichia coli 30S ribosomal subunits in order to identify the contact sites of these complexes at the molecular level. For this purpose, reversed-phase (RP) HPLC-purified peptide–oligoribonucleotide complexes were submitted to N-terminal amino acid sequencing in order to determine the cross-linked peptide moiety and were analyzed using matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) for calculation of the nucleotide composition of the cross-linked complex. Subsequently, for nucleotide sequence information the complexes were partially hydrolyzed or treated with exonucleases and analyzed again by MALDI-MS. Applying this technique, we were able to identify the cross-linked oligoribonucleotide parts in contact with distinct peptide regions derived from ribosomal proteins S4, S7, S8, and S17 from E. coli. 相似文献
11.
PEGylated conjugate of microcrystalline cellulose (MCC) was synthesized by reacting MCC with polyethylene glycol (PEG) 200
in the presence of catalyst at elevated temperature. Conjugation between MCC and PEG was confirmed by FT-IR and 1H NMR studies. The conjugate showed 61% PEG content increase in molecular weight determined by mass spectroscopy. PEGylation
did not improve solubility of cellulose significantly. The physico-chemical properties of conjugate were compared against
MCC. This conjugate was evaluated for water vapor uptake isotherms, maximum water saturation, water penetration rate, disintegration
time, superdisintegration power, and dissolution study. After comparing its results with that of commercial superdisintegrants,
it can be concluded that MCC–PEG conjugate can prove to be a good superdisintegrant. 相似文献
12.
13.
14.
15.
Ygara S. Mendes Nathalia S. Alves Theo L. F. Souza Ivanildo P. Sousa Jr. M. Lucia Bianconi Rafael C. Bernardi Pedro G. Pascutti Jerson L. Silva Andre M. O. Gomes Andréa C. Oliveira 《PloS one》2012,7(10)
Membrane fusion is a crucial step in flavivirus infections and a potential target for antiviral strategies. Lipids and proteins play cooperative roles in the fusion process, which is triggered by the acidic pH inside the endosome. This acidic environment induces many changes in glycoprotein conformation and allows the action of a highly conserved hydrophobic sequence, the fusion peptide (FP). Despite the large volume of information available on the virus-triggered fusion process, little is known regarding the mechanisms behind flavivirus–cell membrane fusion. Here, we evaluated the contribution of a natural single amino acid difference on two flavivirus FPs, FLAG (98DRGWGNGCGLFGK110) and FLAH (98DRGWGNHCGLFGK110), and investigated the role of the charge of the target membrane on the fusion process. We used an in silico approach to simulate the interaction of the FPs with a lipid bilayer in a complementary way and used spectroscopic approaches to collect conformation information. We found that both peptides interact with neutral and anionic micelles, and molecular dynamics (MD) simulations showed the interaction of the FPs with the lipid bilayer. The participation of the indole ring of Trp appeared to be important for the anchoring of both peptides in the membrane model, as indicated by MD simulations and spectroscopic analyses. Mild differences between FLAG and FLAH were observed according to the pH and the charge of the target membrane model. The MD simulations of the membrane showed that both peptides adopted a bend structure, and an interaction between the aromatic residues was strongly suggested, which was also observed by circular dichroism in the presence of micelles. As the FPs of viral fusion proteins play a key role in the mechanism of viral fusion, understanding the interactions between peptides and membranes is crucial for medical science and biology and may contribute to the design of new antiviral drugs. 相似文献
16.
Yang Zhou Zhong Ni Keping Chen Haijun Liu Liang Chen Chaoqun Lian Lirong Yan 《The protein journal》2013,32(7):568-578
17.
Keishi Yamasaki Victor Tuan Giam Chuang Toru Maruyama Masaki Otagiri 《Biochimica et Biophysica Acta (BBA)/General Subjects》2013
Background
Human serum albumin acts as a reservoir and transport protein for endogenous (e.g. fatty acids or bilirubin) and exogenous compounds (e.g. drugs or nutrients) in the blood. The binding of a drug to albumin is a major determinant of its pharmacokinetic and pharmacodynamic profile.Scope of review
The present review discusses recent findings regarding the nature of drug binding sites, drug-albumin binding in certain diseased states or in the presence of coadministered drugs, and the potential of utilizing albumin–drug interactions in clinical applications.Major conclusions
Drug–albumin interactions appear to predominantly occur at one or two specific binding sites. The nature of these drug binding sites has been fundamentally investigated as to location, size, charge, hydrophobicity or changes that can occur under conditions such as the content of the endogenous substances in question. Such findings can be useful tools for the analysis of drug–drug interactions or protein binding in diseased states. A change in protein binding is not always a problem in terms of drug therapy, but it can be used to enhance the efficacy of therapeutic agents or to enhance the accumulation of radiopharmaceuticals to targets for diagnostic purposes. Furthermore, several extracorporeal dialysis procedures using albumin-containing dialysates have proven to be an effective tool for removing endogenous toxins or overdosed drugs from patients.General significance
Recent findings related to albumin–drug interactions as described in this review are useful for providing safer and efficient therapies and diagnoses in clinical settings. This article is part of a Special Issue entitled Serum Albumin. 相似文献18.
Bao Daocheng Bian Hongliang Xu Darong Zhao Chunyang Jin Qing Zhu Min Tao Tingting Cai Jinlan 《International journal of peptide research and therapeutics》2019,25(3):1087-1093
International Journal of Peptide Research and Therapeutics - Human respiratory syncytial virus (RSV) is a primary cause of lower respiratory tract infections and hospital visits during infancy and... 相似文献
19.
Antonia Nicole Klein Tamar Ziehm Markus Tusche Johan Buitenhuis Dirk Bartnik Annett Boeddrich Thomas Wiglenda Erich Wanker Susanne Aileen Funke Oleksandr Brener Lothar Gremer Janine Kutzsche Dieter Willbold 《PloS one》2016,11(4)
The aggregation of amyloid-β (Aβ) is postulated to be the crucial event in Alzheimer’s disease (AD). In particular, small neurotoxic Aβ oligomers are considered to be responsible for the development and progression of AD. Therefore, elimination of thesis oligomers represents a potential causal therapy of AD. Starting from the well-characterized d-enantiomeric peptide D3, we identified D3 derivatives that bind monomeric Aβ. The underlying hypothesis is that ligands bind monomeric Aβ and stabilize these species within the various equilibria with Aβ assemblies, leading ultimately to the elimination of Aβ oligomers. One of the hereby identified d-peptides, DB3, and a head-to-tail tandem of DB3, DB3DB3, were studied in detail. Both peptides were found to: (i) inhibit the formation of Thioflavin T-positive fibrils; (ii) bind to Aβ monomers with micromolar affinities; (iii) eliminate Aβ oligomers; (iv) reduce Aβ-induced cytotoxicity; and (v) disassemble preformed Aβ aggregates. The beneficial effects of DB3 were improved by DB3DB3, which showed highly enhanced efficacy. Our approach yielded Aβ monomer-stabilizing ligands that can be investigated as a suitable therapeutic strategy against AD. 相似文献
20.
Juan Manuel Ferrer María Jesús Leiton Ana María Lourdes Zatón 《Journal of Protein Chemistry》1998,17(2):115-119
The binding of several benzopyranes to serum albumin was studied by equilibrium dialysis at pH7.4 in a 67mM sodium phosphate buffer at 37°C. The equilibrium data were analyzed using a computer program for curve fitting. The binding isotherm for warfarin, 4-hydroxycoumarin, 4-chromanol, coumarin, 3-acetylcoumarin, and benzoic acid can be described by two stoichiometric dissociation constants. Elimination of the 4-hydroxyl group in the coumarin chemical structures decreases the binding affinity of the compounds on the primary binding site of serum albumin, with 4-chromanol the smallest ligand which binds to seroalbumin with high affinity. Thus, the affinity of 4-benzopyranol and the 4-hydroxybenzopyranones greater than that of benzopyranones. On the other hand, elimination of the 2-oxo group in the benzopyranone chemical structures decreases affinity for the secondary binding site. 相似文献