Search results for " Competitive"
showing 10 items of 237 documents
The Role of Innovation in Sustainable Regional Development
2020
Innovation–it is a term that we use for decades, but true meaning of this term changes also for decades, according to dynamic environment we are living in. There is now beginning of the4thindustrial revolution and what has been said in World Economic forum, issues are not about technologies anymore, they are about society. Innovation and entrepreneurship in regions is one of essential tools, in added value creation in economics and in development in national level. It is very important to encourage creativity, new ways of thinking and continuous process of learning of individuals. Aim of the current paper is to investigate development of application of innovations evaluated internationally …
Stereospecific interaction of bicuculline with specific [3H]strychnine binding to rat spinal cord synaptosomal membranes
1980
The gamma-aminobutyric acid (GABA) antagonist (+/-)-bicuculline inhibits specific [3H]strychnine binding to postsynaptic glycine receptor sites in rat spinal cord synaptosomal membranes with an inhibition constant of about 5 microM, which is fairly similar to its inhibition constant reported for the GABA receptor. This effect is highly stereospecific, since the affinity of (-)-bicuculline for the specific [3H]strychnine binding sites is more than ten times less than that of the pharmacologically active (+)-bicuculline. Besides an unspecific effect at the glycine receptor, the results could suggest that the glycine and the GABA receptors are located close together in spinal cord membranes, s…
Synthesis and evaluation of a glibenclamide glucose-conjugate: a potential new lead compound for substituted glibenclamide derivatives as islet imagi…
2007
The search for novel SUR1-ligands originates from the idea to influence the in vivo behaviour by adding new structural moieties to the glibenclamide structure while preserving its binding affinity. Important application of novel conjugates might be their use as radioactively labelled tracer probes in the non-invasive investigation of the islet mass. It is known that the imaging quality of a tracer could be improved by increasing its hydrophilicity, which leads to a reduced plasma protein binding and diminished the unspecific uptake by various organs. In this study the glucose molecule was chosen as a substitute of glibenclamide to enhance hydrophilicity. As expected glucose conjugation lead…
The asialoglycoprotein receptor mediates hepatic binding and uptake of natural hepatitis B virus particles derived from viraemic carriers.
1994
As a putative mechanism of hepatitis B virus (HBV) uptake into hepatocytes the interaction between HBV and the hepatic, human-derived asialoglycoprotein receptor (ASGPR) was investigated. Sera from patients with different variations of hepatitis B surface antigen-(HBsAg) positive chronic hepatitis, HBV particles isolated from HBV carriers with high-titre viraemia and commercial HBsAg served as sources of HBV. ASGPR was affinity-purified from human liver. HBV that had bound to isolated ASGPR was either detected by radio-immunoassay using solid-phase bound ASGPR or enzyme immunoassay with biotin-ASGPR bound to immobilized HBV. Furthermore, binding and uptake of purified, 125I-labelled HBV par…
Immunohistochemical localization of polysialic acid in tissue sections: differential binding to polynucleotides and DNA of a murine IgG and a human I…
1990
For immunolocalization of alpha(2-8)-linked polysialic acid, which forms part of the neural cell adhesion molecule (N-CAM), two monoclonal antibodies, MAb735 and IgMNOV, were employed. Both antibodies have previously been shown to bind the extremely low immunogenic capsular polysaccharide of group B meningococci, which also consists of alpha(2-8) polysialic acid, but not to other, even closely related forms of polysialic acid. Despite the identical polysaccharide specificity of these two MAb, we observed marked differences of the staining pattern in tissue sections. We showed that these differences in immunostaining were due to the crossreactivity of IgMNOV with polynucleotides and DNA. MA…
Characterization of Acylating and Deacylating Activities of an Extracellular Phospholipase A2 in a Water-Restricted Environment
1994
The behavior of porcine pancreatic phospholipase A2 (ppPLA2) in monophasic low-water media has been explored, for the first time, in a systematic manner. It has been investigated how a number of variables can modulate both acylating and deacylating activities of the enzyme, and several interesting, unexpected results are presented. Among the most relevant, when placing ppPLA2 in the water-restricted environment, are the following: (i) it displays a remarkable alteration of its specificity toward the substrate polar head relative to all-water medium; (ii) it is quite severely inhibited by lysophosphatidylcholine (LPC), which has important implications, particularly concerning its acylation a…
Production of specific antibodies and development of a non-isotopic immunoassay for carbamazepine by the carbonyl metallo-immunoassay (CMIA) method.
1995
Abstract As part of our ongoing work to extend the range of applications of the non-isotopic carbonyl metalloimmunoassay (CMIA), previously developed in our laboratory, we describe here the first CMIA study of carbamazepine. The CMIA method uses a metal carbonyl complex as a non-isotopic tracer, and in this case we chose to employ the dicobalt hexacarbonyl moiety (Co2(CO)6) attached to an alkyne. Two organometallic tracers, 3 and 7 , were synthesized, differentiated by the nature and length of the spacer arm of the Co2(CO)6 moiety. Two different coupling methods were subsequently used to synthesize the immunogens 1 and 2, the first one used a carbodiimide, while the second, employed dimethy…
Inhibition of Transfer to Secondary Receptors by Heparan Sulfate-Binding Drug or Antibody Induces Noninfectious Uptake of Human Papillomavirus
2007
ABSTRACT Infection with various human papillomaviruses (HPVs) induces cervical cancers. Cell surface heparan sulfates (HS) have been shown to serve as primary attachment receptors, and molecules with structural similarity to cell surface HS, like heparin, function as competitive inhibitors of HPV infection. Here we demonstrate that the N , N ′-bisheteryl derivative of dispirotripiperazine, DSTP27, efficiently blocks papillomavirus infection by binding to HS moieties, with 50% inhibitory doses of up to 0.4 μg/ml. In contrast to short-term inhibitory effects of heparin, pretreatment of cells with DSTP27 significantly reduced HPV infection for more than 30 h. Using DSTP27 and heparinase, we fu…
Low Density Lipoprotein Receptor-related Protein (LRP) Interacts with Presenilin 1 and Is a Competitive Substrate of the Amyloid Precursor Protein (A…
2005
Presenilin 1 (PS1) is a critical component of the gamma-secretase complex, which is involved in the cleavage of several substrates including the amyloid precursor protein (APP) and the Notch receptor. Recently, the low density receptor-related protein (LRP) has been shown to be cleaved by a gamma-secretase-like activity. We postulated that LRP may interact with PS1 and tested its role as a competitive substrate for gamma-secretase. In this report we show that LRP colocalizes and interacts with endogenous PS1 using coimmunoprecipitation and fluorescence lifetime imaging microscopy. In addition, we found that gamma-secretase active site inhibitors do not disrupt the interaction between LRP an…
Hydantoin-substituted 4,6-dichloroindole-2-carboxylic acids as ligands with high affinity for the glycine binding site of the NMDA receptor.
2002
A novel series of C-3 substituted 4,6-dichloroindole-2-carboxylic acids was synthesized to investigate the influence of different hydrogen-bond donor and acceptor groups at this specific position on the affinity to the glycine site of the NMDA receptor. These novel 3-indolylmethyl derivatives with ring-open (amines, sulfonamides, amides, ureas) and cyclic substituents (imidazolidin-2-ones, (thio)hydantoins) led to the discovery that compounds bearing a hydantoin substituent at the C-3 position of the indole nucleus are the most promising ones. In this series the hydantoins, ureas, and imidazolidin-2-ones were identified as very potent inhibitors of the binding of the glycine site specific l…