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PubMed Journals Articles About "PEGylation Glycosaminoglycan Binding Dominant Negative CXCL8 Mutant Retains" RSS

02:17 EST 20th January 2020 | BioPortfolio

PEGylation Glycosaminoglycan Binding Dominant Negative CXCL8 Mutant Retains PubMed articles on BioPortfolio. Our PubMed references draw on over 21 million records from the medical literature. Here you can see the latest PEGylation Glycosaminoglycan Binding Dominant Negative CXCL8 Mutant Retains articles that have been published worldwide.

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Showing "PEGylation glycosaminoglycan binding dominant negative CXCL8 mutant retains" PubMed Articles 1–25 of 16,000+

PEGylation of a glycosaminoglycan-binding, dominant-negative CXCL8 mutant retains bioactivity in vitro and in vivo.

We have recently shown that a dominant-negative mutant of CXCL8, dnCXCL8, with increased glycosaminoglycan (GAG) binding affinity and inactivated GPCR signaling function is able to efficiently prevent neutrophil infiltration into murine lungs (Adage et al., 2015). Here we present evidence that chemical PEGylation of dnCXCL8 with 20 kDa and 40 kDa PEG does not significantly interfere with GAG binding affinity, nor does it influence the mutant's disabled chemotaxis function, while it strongly improved bioav...


Unraveling the evolutionary origin of ELR motif using fish CXC chemokine CXCL8.

Chemokines are chemotactic proteins involved in host defense through the migration of immune-regulatory cells to the site of infection. Interleukin-8 (CXCL8/IL8) is the most studied "ELR-CXC chemokine/neutrophil activating chemokine (NAC) that regulate neutrophil trafficking during infections and inflammation by binding to its cognate G-protein coupled receptors CXCR1/CXCR2. The "ELR" motif of NAC chemokines is essential for the CXCR1/CXCR2 receptor activation. In order to understand the evolutionary origin...

Mammalian target of rapamycin and p70S6K mediate thrombin-induced nuclear factor-κB activation and IL-8/CXCL8 release in human lung epithelial cells.

Thrombin plays a crucial role in lung inflammatory diseases such as asthma and chronic obstructive pulmonary disease (COPD). Thrombin induces the release of interleukin-8 (IL-8)/CXCL8 by lung epithelial cells, and this phenomenon plays a vital role in lung inflammation. Our previous studies have indicated that thrombin stimulates IL-8/CXCL8 expression through PI3K/Akt/IκB kinase (IKK)α/β/nuclear factor-κB (NF-κB) and p300 pathways in human lung epithelial cells. In the present study, we explored the ro...


Roles of the G protein-coupled receptor kinase 2 and Rab5 in α-adrenergic receptor function and internalization.

Cells expressing eGFP-tagged Rab5 (wild-type or the GDP-Rab5 mutant) and the DsRed-tagged α-adrenergic receptors were employed and the roles of GRK2 were studied utilizing paroxetine and the dominant-negative mutant of GRK2 (DN-GRK2). The following parameters were studied: a) FRET (as an index of α-adrenergic receptor-Rab5 interaction): b) intracellular accumulation of DsRed fluorescence (receptor internalization); c) α-adrenergic receptor phosphorylation, and d) noradrenaline-induced increase in intrace...

A Leishmania donovani Dominant Negative Mutant for eIF2α kinase LdeK1 elicits host-protective immune response.

Dominant negative mutation of LdeK1 gene, an eIF2α kinase from Leishmania donovani revealed its role in translation regulation in response to nutrient starvation earlier. However, whether the kinase influences the infectivity of the parasites which naturally encounters nutrient deprivation during its life cycle was interesting to investigate. Both in vitro and in vivo experiments resulted in decrease of the parasite burden in peritoneal macrophages and in splenic/ hepatic load respectively. An insight into...

Quantitatively fine-tuning the physicochemical and biological properties of peptidic polymers through monodisperse PEGylation.

In biomedicine, PEGylation is one of the most successful strategies to modify the physicochemical and biological properties of peptides, proteins, and other biomacromolecules. Because of the polydisperse nature of regular PEGs and limited PEGylation strategies, it challenging to quantitatively fine-tune and accurately predict the properties of biomacromolecules after PEGylation. However, such fine-tuning and prediction may be crucial for their biomedical applications. Herein, some monodisperse PEGylation st...

Influence of PEGylation on the strength of protein surface salt bridges.

Conjugation of polyethylene glycol (PEGylation) is a well-known strategy for extending the serum half-life of protein drugs and for increasing their resistance to proteolysis and aggregation. We previously showed that PEGylation can increase protein conformational stability; the extent of PEG-based stabilization depends on the PEGylation site, the structure of the PEG-protein linker, and the ability of PEG to release water molecules from the surrounding protein surface to bulk solvent. The strength of a non...

Effect of Glycosaminoglycans on Pathogenic Properties Far-Eastern Tick-Borne Encephalitis Virus.

We studied the effect of sulfated glycosaminoglycan on the infection properties of high-virulence Dal'negorsk strain and low-virulence Primorye-437 of tick-borne encephalitis virus. Differences in reproductive activity of these strains and their tropism to the target cells were revealed. Glycosaminoglycan reduced pathogenetic activity of high-virulence strain in vitro, but had no effect on low-virulence strain. The interaction of imperfect virus particles of non-pathogen strain with the glycosaminoglycan le...

Therapeutic potential of ReACp53 targeting mutant p53 protein in CRPC.

p53 is a tumor suppressor that prevents cancer onset and progression, and mutations in the p53 gene cause loss of the tumor suppressor function of the protein. The mutant p53 protein in tumor cells can form aggregates which contribute to the dominant-negative effect over the wild-type p53 protein, causing loss of p53 tumor suppression or gain of novel oncogenic functions. Mutations in p53 have been implicated in the pathogenesis of primary prostate cancer (PCa), and are often detected in recurrent and metas...

Pathogenesis and pathophysiology of autosomal dominant sleep-related hypermotor epilepsy with S284L-mutant α4 subunit of nicotinic ACh receptor.

To study the pathomechanisms of spontaneous epileptic seizures, including carbamazepine (CBZ)-resistant/zonisamide (ZNS)-sensitive seizures, and comorbidity in autosomal dominant sleep-related hypermotor epilepsy (ADSHE), this study determined functional abnormalities in thalamocortical transmission in transgenic rats bearing rat S286L-mutant Chrna4 (S286L-TG) of α4 subunit of nicotinic acetylcholine receptor (nAChR) corresponds to the human S284L-mutant CHRNA4.

Genetic Polymorphisms of CXCL8 (-251) Are Associated with the Susceptibility of Helicobacter pylori Infection Increased the Risk of Inflammation and Gastric Cancer in Thai Gastroduodenal Patients.

CXC Chemokine Ligand 8 (CXCL8) plays an important role in gastric inflammation and in the progression of gastric cancer induced by Helicobacter pylori (H. pylori) infection. The association of CXCL8, CXC Chemokine Receptor 1 (CXCR1), and CXC Chemokine Receptor 2 (CXCR2) polymorphisms with H. pylori infection and gastric cancer progression needs to be investigated in a population within an enigma area consisting of multiple ethnicities, such as Thailand. To analyze the relative risk of H. pylori infection an...

Catalyst-free Click PEGylation reveals substantial mitochondrial ATP synthase sub-unit alpha oxidation before and after fertilisation.

Using non-reducing Western blotting to assess protein thiol redox state is challenging because most reduced and oxidised forms migrate at the same molecular weight and are, therefore, indistinguishable. While copper catalysed Click chemistry can be used to ligate a polyethylene glycol (PEG) moiety termed Click PEGylation to mass shift the reduced or oxidised form as desired, the potential for copper catalysed auto-oxidation is problematic. Here we define a catalyst-free trans-cyclooctene-methyltetrazine (TC...

The most common RNF43 mutant G659Vfs*41 is fully functional in inhibiting Wnt signaling and unlikely to play a role in tumorigenesis.

RNF43 is an E3 ligase that inhibits Wnt signaling by ubiquitinating Wnt receptors for degradation. It is mutated in various cancer types with the most recurrent mutation being the frameshift G659Vfs*41 with frequencies of ~5-8% in colon, stomach and endometrial cancers. This mutation, a deletion of G in a 7-G repeat, has been assumed to encode an inactive enzyme that would lead to increased Wnt signaling and drive tumorigenesis, yet no functional characterization has been reported. We analyzed the distribut...

Role of amino acid residues important for nucleic acid binding in human Translin.

Translin is a multifunctional DNA/RNA binding protein involved in DNA repair and RNA metabolism. It has two basic regions and involvement of some residues in these regions in nucleic acid binding is established experimentally. Here we report the functional role of four residues of basic region II, Y85, R86, H88, R92 and one residue of C terminal region, K193 in nucleic acid binding using substitution mutant variants. CD analysis of the mutant proteins showed that secondary structure was maintained in all th...

The evolutionarily conserved C-terminal peptide of troponin I is an independently configured regulatory structure to function as a myofilament Ca-desensitizer.

The C-terminal end segment of troponin subunit I (TnI) is a structure highly conserved among the three muscle type-specific isoforms and across vertebrate species. Partial deletion or point mutation in this segment impairs cardiac muscle relaxation. In the present study, we characterized the C-terminal 27 amino acid peptide of human cardiac TnI (HcTnI-C27) for its role in modulating muscle contractility. Biologically or chemically synthesized HcTnI-C27 peptide retains an epitope structure in physiological s...

pH-Induced Binding of the Axial Ligand in an Engineered Cu Site Favors the π State.

Cu centers perform efficient long-range electron transfer. The electronic structure of native Cu sites can be described by a double-potential well with a dominant σ* ground state in fast equilibrium with a less populated π ground state. Here, we report a Cu mutant in which a lysine was introduced in the axial position. This results in a highly unstable protein with a pH-dependent population of the two ground states. Deep analysis of the high-pH form of this variant shows the stabilization of the π ground...

Cdr1p highlights the role of the non-hydrolytic ATP-binding site in driving drug translocation in asymmetric ABC pumps.

ATP-binding cassette (ABC) transporters couple ATP binding and hydrolysis to the translocation of allocrites across membranes. Two shared nucleotide-binding sites (NBS) participate in this cycle. In asymmetric ABC pumps, only one of them hydrolyzes ATP, and the functional role of the other remains unclear. Using a drug-based selection strategy on the transport-deficient mutant L529A in the transmembrane domain of the Candida albicans pump Cdr1p; we identified a spontaneous secondary mutation restoring drug-...

Distinct Binding Preferences between Ras and Raf Family Members and the Impact on Oncogenic Ras Signaling.

The Ras GTPases are frequently mutated in human cancer, and, although the Raf kinases are essential effectors of Ras signaling, the tumorigenic properties of specific Ras-Raf complexes are not well characterized. Here, we examine the ability of individual Ras and Raf proteins to interact in live cells using bioluminescence resonance energy transfer (BRET) technology. We find that C-Raf binds all mutant Ras proteins with high affinity, whereas B-Raf exhibits a striking preference for mutant K-Ras. This selec...

Mapping of the binding site for FcμR in human IgM-Fc.

FcμR is a high-affinity receptor for the Fc portion of human IgM. It participates in B cell activation, cell survival and proliferation, but the full range of its functions remains to be elucidated. The receptor has an extracellular immunoglobulin (Ig)-like domain homologous to those in Fcα/μR and pIgR, but unlike these two other IgM receptors which also bind IgA, FcμR exhibits a binding specificity for only IgM-Fc. Previous studies have suggested that the IgM/FcμR interaction mainly involves the Cμ4 ...

End-point modification of recombinant thrombomodulin with enhanced stability and anticoagulant activity.

Thrombomodulin (TM) is an endothelial cell membrane protein that plays essential roles in controlling vascular haemostatic balance. The 4, 5, 6 EGF-like domain of TM (TM) has cofactor activity for thrombin binding and subsequently protein C activation. Therefore, recombinant TM is a promising anticoagulant candidate but has a very short half-life. Ligation of poly (ethylene glycol) to a bioactive protein (PEGylation) is a practical choice to improve stability, extend circulating life, and reduce immunogenic...

Oxygenation reactions catalyzed by the F557V mutant of soybean Lipoxygenase-1: Evidence for two orientations of substrate binding.

Plant lipoxygenases oxygenate linoleic acid to produce 13(S)-hydroperoxy-9Z,11E-octadecadienoic acid (13(S)-HPOD) or 9-hydroperoxy-10Z,12E-octadecadienoic acid (9(S)-HPOD). The manner in which these enzymes bind substrates and the mechanisms by which they control regiospecificity are uncertain. Hornung et al. (Proc. Natl. Acad. Sci. USA96 (1999) 4192-4197) have identified an important residue, corresponding to phe-557 in soybean lipoxygenase-1 (SBLO-1). These authors proposed that large residues in this pos...

Evaluating the ion exchange chromatography for matrix-assisted pegylation and purification of consensus interferon.

Scientists have implemented protein-PEGylation technology for boosting-up the pharmacokinetics and stability of recombinant therapeutic proteins. In present study A: Matrix assisted PEGylation was compared with solution phase PEGylation, B: Matrix assisted PEGylation was performed with different ion exchange resins for impact of chromatography medium on yield and purity of PEGylated product. DEAE Sepharose CL 6B, DEAE Fracto gel and Macro cap Q ion exchange chromatography medium were compared for on column ...

Structural transitions in the RNA 7SK 5' hairpin and their effect on HEXIM binding.

7SK RNA, as part of the 7SK ribonucleoprotein complex, is crucial to the regulation of transcription by RNA-polymerase II, via its interaction with the positive transcription elongation factor P-TEFb. The interaction is induced by binding of the protein HEXIM to the 5' hairpin (HP1) of 7SK RNA. Four distinct structural models have been obtained experimentally for HP1. Here, we employ computational methods to investigate the relative stability of these structures, transitions between them, and the effects of...

Water networks and correlated motions in mutant IDH1 are critical for allosteric inhibitor binding and activity.

Point mutations in human IDH1 can drive malignancies including lower grade gliomas and secondary glioblastomas, chondrosarcomas, and acute myeloid leukemias. These mutations, which usually affect residue R132, ablate the normal activity of catalyzing the NADP+-dependent oxidation of isocitrate to α-ketoglutarate (αKG) while also acquiring a neomorphic activity of reducing αKG to D-2-hydroxyglutarate (D2HG). Mutant IDH1 can be selectively therapeutically targeted due to structural differences that occur i...

Functional importance of αAsp-350 in the catalytic sites of Escherichia coli ATP synthase.

Negatively charged residue αAsp-350 of the highly conserved VISIT-DG sequence is required for Pi binding and maintenance of the phosphate-binding subdomain and for Pi binding in the catalytic sites of Escherichia coli FF ATP synthase. αAsp-350 is situated in close proximity, 2.88 Å and 3.5 Å, to the conserved known phosphate-binding residues αR376 and βR182. αD350 is also in close proximity, 1.3 Å, to another functionally important residue αG351. Mutation of αAsp-350 to Ala, Gln, or Arg resu...


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