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R J Nolte

Publications and source records attributed to R J Nolte.

12 recordsLinked to original sources
PubMed2001

beta -Helical polymers from isocyanopeptides.

Polymerization of isocyanopeptides results in the formation of high molecular mass polymers that fold in a proteinlike fashion to give helical strands in which the peptide chains are arranged in beta-sheets. The beta-helical polymers retain their structure in water and unfold in a cooperative process at elevated temperatures. The peptide architecture in these polymers is a different form of the beta-helix motif found in proteins. Unlike their natural counterparts, which contain arrays of large beta-sheets stacked in a helical fashion, the isocyanopeptide polymers have a central helical core that acts as a director for the beta-sheet-like arrangement of the peptide side arms. The helical structure of these isocyanopeptide polymers has the potential to be controlled through tailoring of the side branches and the hydrogen-bonding network present in the beta-sheets.

Alanine↗
PubMed2001

Molecular clips based on propanediurea: exceptionally high binding affinities for resorcinol guests.

A series of new receptor molecules derived from 2,4,6,8-tetraazabicyclo[3.3.1]nonane-3,7-dione (propanediurea) is described. These molecules possess a cavity which is defined by two nearly parallel aromatic side walls positioned on top of a bis-urea framework. The resulting "U-shaped" clip molecules are ideal hosts for the complexation of flat aromatic guest molecules. The affinity of these new propanediurea based molecular clips for dihydroxybenzene derivatives is exceptionally high, with association constants up to K(a) = 2 400 000 L mol(-)(1). Comparison of the binding mechanism of a variety of clip and half clip hosts, in conjunction with NMR, IR, and X-ray studies, has enabled the reason for this high binding to be elucidated. It is shown that subtle sub-angstrom changes in the geometry of the clip molecules have a great impact on their binding properties.

Journal Article↗
PubMed2001

Synthesis, aggregation, and binding behavior of synthetic amphiphilic receptors.

Amphiphilic bowl-shaped receptor molecules have been synthesized starting from diphenylglycoluril. Upon dispersion in water, these molecules self-assemble to form vesicles that bind neutral guests and alkali metal ions. In the case of bis(alkylester)-modified receptor compound 4, electron microscopy reveals that an increase in the size of the alkali metal ion (from Na(+) or K(+) to Rb(+) and to Cs(+)) leads to a change in the shape of the aggregates, viz. from vesicles to tubules. Monolayer experiments suggest that this behavior is due to a change in the conformation of this amphiphilic receptor. In water, molecules of 4 have an elongated conformation that changes to a sandwich-like one upon binding of alkali metal ions. Binding studies with vesicles from the bis-ammonium receptors 6 and 9 and the guest 4-(4-nitrophenylazo)resorcinol (Magneson) reveal that below the critical aggregation concentration (CAC) of the amphiphile 1:1 host-guest complexes are formed with high host-guest association constants. Above the CAC, a host-guest ratio of 2:1 was observed that indicates that only the cavities on the outside of the vesicle can be occupied. In the case of the naphthalene walled compound 8 changes in the vesicle structure are induced by the organic guest Magneson.

Chloroform↗
PubMed2001

Lamellar organic thin films through self-assembly and molecular recognition.

Molecular clips possessing U-shaped cavities have been functionalized on their convex side with long aliphatic tails. These molecules form dimers which self-assemble into malleable lamellar thin films. Upon addition of a guest (methyl 3,5-dihydroxybenzoate), a 1:1 host-guest complex is formed, which prohibits clip dimerization. As a result, the lamellar structure of the material is lost. Complexation of 3,5-dihydroxybenzoic acid in the clip results in host-guest complexes which dimerize by hydrogen bonding interactions between the carboxylic acid functions of the bound guests. This dimerization restores the lamellar type architecture of the material.

Journal Article↗
PubMed2001

Influence of inflammatory cells and serum on the performance of implantable glucose sensors.

The objective of this investigation was to evaluate the influence of polymorphonuclear granulocytes on the performance of uncoated and cellulose acetate/Nafion coated amperometric glucose sensors in vitro. The response of these sensors was also investigated in serum. Uncoated and coated sensors showed lower sensitivities to glucose, with a significant drift in sensor output upon exposure to serum or leukocytes. Although the use of a coating resulted in higher sensitivity, the progressive loss of output was not completely prevented. Stimulated granulocytes were shown to excrete components, probably catalase and myeloperoxidase, which consumed the hydrogen peroxide formed by the oxidation of glucose. In addition, adsorbed serum proteins formed a diffusional barrier for glucose. Furthermore, serum was found to contain low-molecular weight components that alone inhibited glucose oxidase activity. Based on preliminary electrochemical results, we postulate that rabbit serum contains oxidizing substrates that compete with molecular oxygen for the acceptance of electrons from the oxidized enzyme. Consequently, future efforts should be aimed at elucidating the mechanisms involved in the interference of unknown serum components with electron transfer. In addition, further investigations have to be performed to develop an outer membrane that minimizes protein adsorption as well as the actions of inflammatory cells.

Animals↗
PubMed2001

A percutaneous device as model to study the in vivo performance of implantable amperometric glucose sensors.

Glucose kinetics were investigated in subcutaneous tissue of rabbits, in which a percutaneous device was implanted. The device was used for collection of tissue fluid and as carrier of an amperometric glucose sensor. Changes in glycaemia were reflected in subcutaneous tissue fluid. However, a limited number of responses of the implanted sensors were observed. Histologic evaluation showed thin fibrous capsules surrounding the implants. Accumulations of inflammatory cells were observed inside the subcutaneous chamber. The experiments again showed that changes in blood glucose concentration can be measured in subcutaneous tissue fluid collected with a percutaneous device. Nevertheless, implanted glucose sensors could not reliably monitor these changes. Supported by our histological observations and sufficient in vitro performance, we suppose that the cellular reaction to the sensor plays an important role in this poor in vivo performance. In combination with adsorption of tissue fluid proteins, this results in a reversible deactivation of implanted sensors. The exact mechanisms involved in this process are currently unknown and need further investigation.

Journal Article↗
PubMed2000

Biocompatibility evaluation of sol-gel coatings for subcutaneously implantable glucose sensors.

The objective of the current investigation is to determine the soft-tissue biocompatibility of sol-gel matrices which can be used to optimize the properties of implantable glucose sensors. The biocompatibility of sol-gel matrices with heparin, dextran sulphate, Nafion, polyethylene glycol, and polystyrene sulphonate was examined in vitro in simulated body fluid and with cell culture experiments using human dermal fibroblasts. Finally, an in vivo study was performed. Therefore, sol-gel coated polystyrene discs were inserted subcutaneously in the back of rabbits. After 4 and 12 weeks, the implants with surrounding tissue were retrieved and processed histologically. In simulated body fluid, the formation of a granular calcium phosphate precipitate was observed. Cell proliferation on polyethylene glycol, Nafion, and heparin coated substrates was comparable to control samples and significantly higher than on dextran sulphate and polystyrene sulphate coated substrates. Light microscopic evaluation of the retrieved in vivo samples showed a fair tissue reaction to all materials. Histomorphometric analysis demonstrated that there were no differences in tissue response to the different sol-gel coatings. In conclusion, sol-gel matrices exhibit a fair biocompatibility both in vitro and in vivo. These results will form the basis for further research into the real merits of sol-gel coatings in optimizing the properties of subcutaneously implantable glucose sensors.

Animals↗
PubMed1994

Highly stable first-generation biosensor for glucose utilizing latex particles as the enzyme-immobilizing matrix.

The ability of polystyrene latex beads to immobilize glucose oxidase was applied to construct a stable biosensor for glucose. This biosensor measures glucose by detecting the hydrogen peroxide produced by the enzyme. The biosensor performance was studied by amperometry. Glucose concentrations ranging from 1 to 50mM can be measured with this sensor. The sensor is active over a broad range of pH and is very stable, which makes it suitable for a number of possible applications.

Biosensing Techniques↗
PubMed1988

Kinetics and thermodynamics of ethanol oxidation catalyzed by genetic variants of the alcohol dehydrogenase from Drosophila melanogaster and D. simulans.

Four naturally occurring variants of the alcohol dehydrogenase enzyme (ADH; EC 1.1.1.1) from Drosophila melanogaster and D. simulans, with different primary structures, have been subjected to kinetic studies of ethanol oxidation at five temperatures. Two amino acid replacements in the N-terminal region which distinguish the ADH of D. simulans from the three ADH allozymes of D. melanogaster generate a significantly different activation enthalpy and entropy, and Gibbs free energy change. The one or two amino acid replacements in the C-terminal region between the ADH allozymes of D. melanogaster do not have such clear-cut effects. All four ADH variants show highly negative activation entropies. Sarcosine oxidation by the ADH-71k variant of D. melanogaster has an activation energy barrier similar to that of ethanol oxidation. Three amino acid differences between the ADH of D. simulans and the ADH-F variant of D. melanogaster influence the kappa cat and kappa cat/Kethm constant by a maximum factor of about 2 and 2.5, respectively, over the whole temperature range. Product inhibition patterns suggest a 'rapid equilibrium random' mechanism of ethanol oxidation by the ADH-71k, and the ADH of D. simulans.

Alcohol Dehydrogenase↗
PubMedDate not supplied

Performance of subcutaneously implanted glucose sensors: a review.

Despite a considerable amount of research attributed to the development of an implantable glucose sensor, to date there is no clinically applicable concept for continuous glucose monitoring. Investigations to validate the subcutaneous tissue for continuous glucose sensing mostly comprise short-term implantations of glucose sensors. Most implanted glucose sensors showed a significant decay in sensitivity over the implantation period. This bioinstability was not to be expected from the in vitro performance of the sensors. In this article, the influence of possible failure mechanisms on the poor in vivo performance of subcutaneously implanted glucose sensors is reviewed.

Animals↗