Search results for "binding"
showing 10 items of 3896 documents
Efficacy of levetiracetam in the treatment of drug-resistant Rett Syndrome.
2010
Rett syndrome (RTT) is a progressive neurological disorder characterized by a wide spectrum of phenotypes. Epilepsy is reported to occur in 50–90% of patients with RTT; some develop medically refractory epilepsy. The aim of this study is to investigate the efficacy of levetiracetam (LEV) in drug-resistant patients with RTT. This prospective, pragmatic, open-label study consisted of an 8-week baseline period and a 6-month evaluation period. Efficacy variable was the mean frequency of monthly seizures before, and after 3 and 6 months of treatment with LEV. Eight female patients, aged 7.5–19 years (M12.8 ± 5) entered the study. Mean age at epilepsy onset was 25.8 ± 14.1 months. All patients sh…
Peptidomimetics – An infinite reservoir of metal binding motifs in metabolically stable and biologically active molecules
2020
The involvement of metal ions in interactions with therapeutic peptides is inevitable. They are one of the factors able to fine-tune the biological properties of antimicrobial peptides, a promising group of drugs with one large drawback - a problematic metabolic stability. Appropriately chosen, proteolytically stable peptidomimetics seem to be a reasonable solution of the problem, and the use of D-, β-, γ-amino acids, unnatural amino acids, azapeptides, peptoids, cyclopeptides and dehydropeptides is an infinite reservoir of metal binding motifs in metabolically stable, well-designed, biologically active molecules. Below, their specific structural features, metal-chelating abilities and anti…
Single Peptide Backbone Surrogate Mutations to Regulate Angiotensin GPCR Subtype Selectivity
2020
Mutating the side-chains of amino acids in a peptide ligand, with unnatural amino acids, aiming to mitigate its short half-life is an established approach. However, it is hypothesized that mutating specific backbone peptide bonds with bioisosters can be exploited not only to enhance the proteolytic stability of parent peptides, but also to tune its receptor subtype selectivity. Towards this end, four [Y]6-Angiotensin II analogues are synthesized where amide bonds have been replaced by 1,4-disubstituted 1,2,3-triazole isosteres in four different backbone locations. All the analogues possessed enhanced stability in human plasma in comparison with the parent peptide, whereas only two of them a…
Structure, mechanism and regulation of peroxiredoxins.
2003
Peroxiredoxins (Prxs) are a ubiquitous family of antioxidant enzymes that also control cytokine-induced peroxide levels which mediate signal transduction in mammalian cells. Prxs can be regulated by changes to phosphorylation, redox and possibly oligomerization states. Prxs are divided into three classes: typical 2-Cys Prxs; atypical 2-Cys Prxs; and 1-Cys Prxs. All Prxs share the same basic catalytic mechanism, in which an active-site cysteine (the peroxidatic cysteine) is oxidized to a sulfenic acid by the peroxide substrate. The recycling of the sulfenic acid back to a thiol is what distinguishes the three enzyme classes. Using crystal structures, a detailed catalytic cycle has been deriv…
The analysis of modified peroxisome proliferator responsive elements of the peroxisomal bifunctional enzyme in transfected HepG2 cells reveals two re…
1995
AbstractPeroxisome proliferators (PPs) are non-genotoxic carcinogens in rodents. They can induce the expression of numerous genes via the heterodimerization of two members of the steroid hormone receptor superfamily, called the peroxisome proliferator-activated receptor (PPAR) and the 9-cis retinoic acid receptor (RXR). Many of the PP responsive genes possess a peroxisome proliferator response element (PPRE) formed by two TGACCT-related motifs. The bifunctional enzyme (HD) PPRE contains 3 such motifs, creating DR1 and DR2 sequences. PPAR and RXR regulate transcription via the DR1 element while DR2 modulates the expression of the gene via auxiliary factors in HepG2 cells.
Functional characterization of a peroxisome proliferator response-element located in the intron 3 of rat peroxisomal thiolase B gene.
2003
Expression of the rat peroxisomal 3-ketoacyl-CoA thiolase gene B is induced by peroxisome proliferators. Although a sequence element like a peroxisome proliferator-activated receptor (PPAR)-binding site is located in the promoter region of this gene, we previously found that this element is competent for the activation by hepatocyte nuclear factor-4, but not functional with PPARalpha. We describe here a new peroxisome proliferator-response element located in the intron 3 (+1422/+1434) that binds in vitro the PPARalpha/retinoid X receptor alpha heterodimer and confers the induction by PPARalpha in transfection assays. We propose a model of regulation of the rat thiolase B gene involving thos…
Enhanced baculovirus-mediated transduction of human cancer cells by tumor-homing peptides.
2006
ABSTRACT Tumor cells and vasculature offer specific targets for the selective delivery of therapeutic genes. To achieve tumor-specific gene transfer, baculovirus tropism was manipulated by viral envelope modification using baculovirus display technology. LyP-1, F3, and CGKRK tumor-homing peptides, originally identified by in vivo screening of phage display libraries, were fused to the transmembrane anchor of vesicular stomatitis virus G protein and displayed on the baculoviral surface. The fusion proteins were successfully incorporated into budded virions, which showed two- to fivefold-improved binding to human breast carcinoma (MDA-MB-435) and hepatocarcinoma (HepG2) cells. The LyP-1 pepti…
Peptide microarrays enable rapid mimotope optimization for pharmacokinetic analysis of the novel therapeutic antibody IMAB362.
2014
As membrane proteins play an important role in a variety of life-threatening diseases, the development of therapeutic monoclonal antibodies against membrane proteins is of significant interest. Among many other requirements, the process of antibody drug development requires a set of tailor-made assays for the characterization of the antibodies and for monitoring their activity. Designing assays to characterize antibodies directed to membrane proteins is challenging, because the natural targets are often not available in a format that is compatible with a biochemical assay setup. Thus, alternatives that mimic the targeted membrane proteins are needed. In this study, we developed optimal pept…
Identification of pH-regulated antigen 1 released from Candida albicans as the major ligand for leukocyte integrin alphaMbeta2.
2007
Candida albicans is a common opportunistic fungal pathogen and is the leading cause of invasive fungal disease in immunocompromised individuals. The induction of cell-mediated immunity to C. albicans is of critical importance in host defense and the prime task of cells of the innate immune system. We previously demonstrated that the integrin alpha(M)beta(2) (CD11b/CD18) is the major leukocyte receptor involved in C. albicans recognition, mediating both adhesive and migratory responses to the fungus. In the present study, we demonstrate that various C. albicans strains release a protease-sensitive activity into their conditioned medium that supports alpha(M)beta(2)-mediated cell adhesion and…
A novel peripherally restricted cannabinoid receptor antagonist, AM6545, reduces food intake and body weight, but does not cause malaise, in rodents
2010
BACKGROUND AND PURPOSE Cannabinoid CB1 receptor antagonists reduce food intake and body weight, but clinical use in humans is limited by effects on the CNS. We have evaluated a novel cannabinoid antagonist (AM6545) designed to have limited CNS penetration, to see if it would inhibit food intake in rodents, without aversive effects. EXPERIMENTAL APPROACH Cannabinoid receptor binding studies, cAMP assays, brain penetration studies and gastrointestinal motility studies were carried out to assess the activity profile of AM6545. The potential for AM6545 to induce malaise in rats and the actions of AM6545 on food intake and body weight were also investigated. KEY RESULTS AM6545 binds to CB1 recep…