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C J Edge

Publications and source records attributed to C J Edge.

32 records · Page 2Linked to original sources
PubMed1992

Fast sequencing of oligosaccharides: the reagent-array analysis method.

A method of oligosaccharide analysis involving controlled fragmentation resulting from enzymatic digestion is presented. The principle involves generating a set of fragments from the original oligosaccharides, characterizing them in terms of their hydrodynamic volumes, determining their molar proportions, and identifying the oligosaccharides by comparison with a computer-generated data base. Experimentally, this technique involves incubation of aliquots of a sample with a set of defined mixtures of exoglycosidases followed by pooling of the products and a single analysis on the product pool. This method has several practical advantages over current techniques, including speed and the ability to use smaller amounts of starting material. The detection of the intensity-versus-hydrodynamic volume profile is limited only by the specific activity of the labeling method. The ability to perform the enzyme digestions is limited by the individual Km values of the enzymes.

Carbohydrate Sequence↗
PubMed1991

The solution conformation of the Le chi group.

The solution conformation of the non-reducing terminal Gal beta 1----4 (Fuc alpha 1----3)GlcNAc (Lewis X or Le chi) group in the oligosaccharide Lacto-N-fucopentaose (LNFP) III has been determined by high resolution 1H NMR spectroscopy and semi-empirical quantum mechanical calculations. The two methods give the same single conformer for the Le chi group showing close packing of the Gal and Fuc rings. The metal binding properties and homotypic oligomer formation of LNFP III have also been investigated by NMR spectroscopy. No evidence for metal binding or high-affinity homotypic oligomer formation has been found.

Carbohydrate Conformation↗
PubMed1991

The conformational effects of N-glycosylation on the tailpiece from serum IgM.

1H-NMR spectroscopy has been used to study the conformation and dynamics of the isolated tailpiece from human serum immunoglobulin M, a 22-residue peptide containing a single asparagine glycosylation site. The peptide is isolated as a set of glycoforms, varying only in the sequence of the oligosaccharide attached at the glycosylation site. The oligosaccharides present have the general formula (Man)n(GlcNAc)2, with 45% having n = 6, 45% having n = 8 and 10% having n = 7 and/or 9. They have been identified and their NMR parameters compared to those found for the isolated oligosaccharides in free solution. The conformation and dynamics of the peptide component have also been studied, using NOE data and hydrogen-exchange experiments, and the results compared to those obtained from the aglycosyl peptide of the same sequence. The presence of the peptide is found to have no measurable effect on the conformation of the oligosaccharides. However, the presence of oligosaccharide causes a decrease in the conformational mobility of the backbone and sidechains of the peptide in the region of the glycosylation site. This is proposed to result from interactions between the oligosaccharide core and the amino acid side chains. Further, the conformation of the N-glycosidic linkage has been shown to be both rigid and planar. Thus, the conformational space available to an N-linked oligosaccharide in a glycoprotein relative to the protein may depend to a large extent upon the flexibility of the asparagine side chain. Various roles for the different glycoforms of the tail peptide are discussed.

Amino Acid Sequence↗
PubMed1991

Complications of pharyngostomy.

An account is given of a fatal complication following the use of a pharyngostomy feeding tube. The literature on this topic is reviewed with regard to complications. Of the 671 patients that have been reported previously there have been no fatal or serious complications and minor complications were reported in only 42 patients. We regard the technique of pharyngostomy to be safe but recommendations are made to avoid the complication reported here.

Aged↗
PubMed1990

Uncertainties in structural determinations of oligosaccharide conformation, using measurements of nuclear Overhauser effects.

A fundamental problem in the determination of molecular structure by n.m.r. spectroscopy is insufficient experimental constraints. This problem is particularly marked for oligosaccharides, where few constraints are available across glycosidic linkages. By calculating distances as a function of dihedral angle, it is shown that, in general, two n.O.e. constraints result in two possible conformations for each glycosidic linkage, one of which can usually be discarded on the basis of model building or energy calculations. Using these calculations, an estimate of the uncertainty in the structure can be obtained.

Carbohydrate Conformation↗
PubMed1990

500-picosecond molecular dynamics in water of the Man alpha 1----2Man alpha glycosidic linkage present in Asn-linked oligomannose-type structures on glycoproteins.

Molecular dynamics simulations of the Man alpha 1----2Man alpha glycosidic linkage found in the N-linked glycans of glycoproteins were performed in vacuo and in the presence of water. In the latter case significant dampening of the molecular fluctuations was found when compared to the in vacuo simulation. A 500-ps dynamics simulation in water showed only occasional short-lived deviations from the minimum-energy conformation, more consistent with carbohydrate "breathing" than flexibility. These studies add further evidence that oligosaccharides can maintain "fixed" geometries with relatively long lifetimes and are in agreement with experimental NMR-derived parameters for the same linkage in oligomannose structures.

Carbohydrate Conformation↗
PubMed1990

Primary sequence dependence of conformation in oligomannose oligosaccharides.

The oligomannose series of oligosaccharides from bovine thyroglobulin (BTG) and the variant surface glycoprotein (VSG) of Trypanosoma brucei have been isolated and sequenced by 1H NMR. The structure of Man9GlcNAc2, the parent molecule of the series, is shown below. Structural isomerism occurs within this series through the removal of residues D1, D2, D3, and C. Using spin-spin coupling and chemical shift data the rotamer distributions about the dihedral angle omega for the Man alpha 1-6Man beta and Man alpha 1-6Man alpha linkages were determined for each member of the series. It is shown that the dihedral angle omega of the Man alpha 1-6Man beta linkage exhibits low flexibility with a preference for the omega = 180 degrees conformation when residue D2 is present and high flexibility when this residue is absent. Flexibility of omega for the Man alpha 1-6Man alpha is largely independent of primary sequence and is intermediate between the two Man alpha 1-6Man beta extremes, again with a preference for the omega = 180 degrees conformation. [see text] There are, however, data which indicate that removal of residue D3 may confer additional flexibility upon the dihedral angle omega of the Man alpha 1-6Man alpha linkage. Molecular graphics modelling, together with chemical and enzymatic modification studies, suggest that the origin of the observed primary sequence dependence of the Man alpha 1-6Man beta linkage arises from steric factors. On the basis of these observations taken together with previous work, it is postulated that recognition of individual oligomannose conformations may play a role in the control of N-linked oligosaccharide biosynthesis.

Carbohydrate Conformation↗
PubMed1989

Solution structure of the glycosylphosphatidylinositol membrane anchor glycan of Trypanosoma brucei variant surface glycoprotein.

The average solution conformation of the glycosylphosphatidylinositol (GPI) membrane anchor of Trypanosoma brucei variant surface glycoprotein (VSG) has been determined by using a combination of two-dimensional 1H-1H NMR methods together with molecular orbital calculations and restrained molecular dynamics simulations. This allows the generation of a model to describe the orientation of the glycan with respect to the membrane. This shows that the glycan exists in an extended configuration along the plane of the membrane and spans an area of 600 A2, which is similar to the cross-sectional area of a monomeric N-terminal VSG domain. Taken together, these observations suggest a possible space-filling role for the GPI anchor that may maintain the integrity of the VSG coat. The potential importance of the GPI glycan as a chemotherapeutic target is discussed in light of these observations.

Animals↗
PubMed1988

Photodynamic therapy and the treatment of head and neck cancer.

An account is given of how Photodynamic Therapy (PDT) may be used in the diagnosis and treatment of cancer of the head and neck. The role and mode of action of the tumour sensitising agent, Haematoporphyrin derivative (HPD), are shown and the current use of lasers as suitable light sources will be discussed. Individual cases are used to illustrate the current state of this form of treatment and an indication of future developments is provided.

Adult↗
PubMedDate not supplied

Scuba diving with diabetes mellitus--the UK experience 1991-2001.

OBJECTIVES: To survey the outcomes and practises of divers with diabetes mellitus. METHODS: Diabetic persons wishing to learn to scuba-dive or established divers who have diabetes mellitus in the UK are requested to fill in a detailed questionnaire annually. Divers are asked to provide basic epidemiological information and general diving history. Data provided by the diver's diabetic physician provided independent evidence of the diver's medical status. These data are recorded and analysed. RESULTS: Data have been gathered from 323 diabetic divers (269 male, 54 female) and 8,760 dives have been recorded over 11 years. Two fatalities were reported, both in non-insulin dependent divers. One incident of hypoglycaemia underwater in an insulin dependent diabetic diver has been reported. CONCLUSIONS: This survey showed that in the group of well-controlled diabetic divers studied, there were no serious problems due to hypoglycaemia when they dived. Long-term complications of diabetes must be excluded before a diabetic diver may be permitted to dive.

Adult↗