Search results for "glycopeptide"
showing 10 items of 164 documents
N-Glycosylation modification of proteins is an early marker of the enterocytic differentiation process of HT-29 cells
1990
International audience; The human colon cancer cell line HT-29 remains totally undifferentiated when glucose is present in the culture medium (HT-29 Glc+), while the same cells may undergo typical enterocytic differentiation after reaching confluence when grown in glucose-deprived medium (HT-29 Glc-). Recently, we demonstrated a deficiency in the overall N-glycan processing in confluent undifferentiated cells, whereas differentiated cells follow a classical pattern of N-glycosylation. The main changes in N-glycosylation observed in confluent undifferentiated cells may be summarised as follows: 1) the conversion of high mannose into complex glycopeptides is greatly decreased; 2) this decreas…
Intravenous BQ-123 and phosphoramidon reduce ventricular ectopic beats and myocardial infarct size in dogs submitted to coronary occlusion and reperf…
2001
Abstract The aim of this work was to investigate the influence of endothelin on myocardial ischemia and reperfusion in anaesthetized dogs. Animals were submitted to left thoracotomy and 120 min of left anterior descending coronary occlusion, followed by 180 min of reperfusion. Arterial blood pressure and electrocardiogram (ECG) were recorded in order to analyze heart rate (HR)–pressure product and production of ectopic beats. Infarcted areas were identified by a macroscopic staining method and infarct size was expressed as percentage of risk zone. To inhibit the effects of endothelin in a group of animals, we administered intravenously an endothelin synthesis inhibitor (phosphoramidon) and …
Fully synthetic self-adjuvanting thioether-conjugated glycopeptide-lipopeptide antitumor vaccines for the induction of complement-dependent cytotoxic…
2012
Glycopeptides of tumor-associated mucin MUC1 are promising target structures for the development of antitumor vaccines. Because these endogenous structures were weakly immunogenic, they were coupled to immune-response-stimulating T-cell epitopes and the Pam(3)Cys lipopeptide to induce strong immune responses in mice. A new thioether-ligation method for the synthesis of two- and three-component vaccines that contain MUC1 glycopeptides as the B-cell epitopes, a T-cell epitope peptide, and the Pam(3)CSK(4) lipopeptide is described. The resulting fully synthetic vaccines were used for the vaccination of mice, either in a liposome with Freund's adjuvant or in aqueous PBS buffer. The three-compon…
Synthesis of Fluorinated Glycosyl Amino Acid Building Blocks for MUC1 Cancer Vaccine Candidates by Microreactor-Assisted Glycosylation
2012
Abstract MUC1-type glycopeptides have already shown their potential as possible cancer vaccine candidates. In addition, first examples of fluorinated antigen structures, especially containing the Thomsen–Friedenreich antigen, with similar antibody recognition have been reported. Using microreactor techniques for improvement of the crucial step, the complex glycosylation reactions, is an efficient way to find optimized reaction parameter as well as to circumvent well-known scale-up drawbacks. Besides, this is the first report of continuous flow glycosylations of glycosyl amino acids, in particular with fluorinated glycosyl building blocks.
Phosphate-controlled regulator for the biosynthesis of the dalbavancin precursor A40926
2007
ABSTRACT The actinomycete Nonomuraea sp. strain ATCC 39727 produces the glycopeptide A40926, the precursor of the novel antibiotic dalbavancin. Previous studies have shown that phosphate limitation results in enhanced A40926 production. The A40926 biosynthetic gene ( dbv ) cluster, which consists of 37 genes, encodes two putative regulators, Dbv3 and Dbv4, as well as the response regulator (Dbv6) and the sensor-kinase (Dbv22) of a putative two-component system. Reverse transcription-PCR (RT-PCR) and real-time RT-PCR analysis revealed that the dbv14 - dbv8 and the dbv30 - dbv35 operons, as well as dbv4 , were negatively influenced by phosphate. Dbv4 shows a putative helix-turn-helix DNA-bind…
Glycopeptide-functionalized gold nanoparticles for antibody induction against the tumor associated mucin-1 glycoprotein
2015
We report the preparation of gold nanoparticle (AuNP)-based vaccine candidates against the tumor-associated form of the mucin-1 (MUC1) glycoprotein. Chimeric peptides, consisting of a glycopeptide sequence derived from MUC1 and the T-cell epitope P30 sequence were immobilized on PEGylated AuNPs and the ability to induce selective antibodies in vivo was investigated. After immunization, mice showed significant MHC-II mediated immune responses and their antisera recognized human MCF-7 breast cancer cells. Nanoparticles designed according to this report may become key players in the development of anticancer vaccines.
Synthesis and Antibody Binding of Highly Fluorinated Amphiphilic MUC1 Glycopeptide Antigens
2011
The analysis of humoral immune responses is of great importance for basic and clinical research. Mapping the structural requirements of epitope recognition with modified tumor-associated carbohydrate antigens allows both the development of biomarkers and the design of synthetic anticancer vaccines. For this purpose, double-tailed hydrocarbon/fluorocarbon membrane anchors have been prepared and conjugated to a TN dipeptide. Furthermore, a novel hydrophobized MUC1 tandem repeat glycopeptide antigen was fully assembled on a solid support and its specific binding to different mouse anti-MUC1 antibodies was demonstrated through ELISA, QCM, and SPR measurements. Such functional fluorous MUC1 anti…
Enhanced immunogenicity of multivalent MUC1 glycopeptide antitumour vaccines based on hyperbranched polymers.
2015
Enhancing the immunogenicity of an antitumour vaccine still poses a major challenge. It depends upon the selected antigen and the mode of its presentation. We here describe a fully synthetic antitumour vaccine, which addresses both aspects. For the antigen, a tumour-associated MUC1 glycopeptide as B-cell epitope was synthesised and linked to the immunostimulating T-cell epitope P2 derived from tetanus toxoid. The MUC1-P2 conjugate is presented multivalently on a hyperbranched polyglycerol to the immune system. In comparison to a related vaccine of lower multivalency, this vaccine exposing more antigen structures on the hyperbranched polymer induced significantly stronger immune responses in…
A fully synthetic glycopeptide antitumor vaccine based on multiple antigen presentation on a hyperbranched polymer.
2014
For antitumor vaccines both the selected tumor-associated antigen, as well as the mode of its presentation, affect the immune response. According to the principle of multiple antigen presentation, a tumor-associated MUC1 glycopeptide combined with the immunostimulating T-cell epitope P2 from tetanus toxoid was coupled to a multi-functionalized hyperbranched polyglycerol by "click chemistry". This globular polymeric carrier has a flexible dendrimer-like structure, which allows optimal antigen presentation to the immune system. The resulting fully synthetic vaccine induced strong immune responses in mice and IgG antibodies recognizing human breast-cancer cells.
Highly regioselective synthesis of a 3-O-sulfonated arabino Lewisa asparagine building block suitable for glycopeptide synthesis
2006
Using the stannylene method, the trisaccharide 2-acetamido-3-O-[6-O-benzyl-beta-D-galactopyranosyl]-4-O-[2,3,4-tri-O-benzyl-beta-D-arabinopyranosyl]-6-O-benzyl-2-deoxy-beta-D-glucopyranosyl azide was regioselectively sulfonated and, after reduction of the anomeric azide, coupled to Fmoc alpha-allyl aspartate. After Pd(0)-catalyzed deallylation, the sulfatyl Lewis(a) asparagine building block was obtained, suitable for solid-phase glycopeptide synthesis applying the fluoride labile PTMSEL linker system.