Lysosomal Storage Diseases Research Papers (original) (raw)

Desalting of sugar samples is essential for the success of many techniques of carbohydrate analysis such as mass spectrometry, capillary electrophoresis, anion exchange chromatography, enzyme degradation and chemical derivatization. All... more

Desalting of sugar samples is essential for the success of many techniques of carbohydrate analysis such as mass spectrometry, capillary electrophoresis, anion exchange chromatography, enzyme degradation and chemical derivatization. All desalting methods which are currently used have limitations: for example, mixed-bed ion-exchange columns risk the loss of charged sugars, precipitation of salt by a non-aqueous solvent can result in co-precipitation of oligosaccharides, and gel chromatography uses highly crosslinked packings in which separation of small oligosaccharides is difficult to achieve. We demonstrate that graphitized carbon as a solid phase extraction cartridge can be used for the purification of oligosaccharides (or their derivatives) from solutions containing one or more of the following contaminants: salts (including salts of hydroxide, acetate, phosphate), monosaccharides, detergents (sodium dodecyl sulfate and Triton X-100), protein (including enzymes) and reagents for ...

Hydrops fetalis (HF) is characterized by an accumulation of fluid in the extracellular compartments and in body cavities. Non-immune HF (NIHF) is caused by a wide variety of disorders and overall, 20–25% of NIHF remain unexplained. Inborn... more

Hydrops fetalis (HF) is characterized by an accumulation of fluid in the extracellular compartments and in body cavities. Non-immune HF (NIHF) is caused by a wide variety of disorders and overall, 20–25% of NIHF remain unexplained. Inborn errors of metabolism, mostly lysosomal storage diseases have been estimated to account for 1–2% of cases, leading to HF by anemia or liver

A thin polymer microchip was coupled with a Fourier transform ion cyclotron resonance (FTICR) 9.4 T mass spectrometer and the method was optimized in negative ion mode for glycopeptide screening. The interface between the polymer... more

A thin polymer microchip was coupled with a Fourier transform ion cyclotron resonance (FTICR) 9.4 T mass spectrometer and the method was optimized in negative ion mode for glycopeptide screening. The interface between the polymer microchip and FTICR mass spectrometer consists of an in-laboratory conceived and designed mounting system that exhibits robust and controllable alignment of the chip toward the inlet of the mass spectrometer. The particular attribute of the polymer chip coupled to the FTICR mass spectrometer, to achieve an increase in ionization efficiency and sensitivity under the premise of high mass accuracy of detection, is highlighted by the large number of major and minor glycopeptide structures detected and identified in highly heterogeneous mixtures obtained from urine matrices. Glycoforms expressing various saccharide chain lengths ranging from tri- to dodecasaccharide, bearing up to three sialic acid moieties, could be detected and assigned based on the accuracy of the mass measurement (average mass deviation below 6 ppm) of their molecular ions. (–)Thin chipESI-FTICRMS is a potent novel system for glycomic screening of complex mixtures, as demonstrated for identification of singly sialylated O-glycosylated amino acids and peptides from urine matrices, and could be considered for general applicability in the glycoanalytical field. Copyright © 2004 John Wiley & Sons, Ltd.

Understanding and controlling carbohydrate processing enzymes (CPE) have been major issues and challenges for chemists, biochemists and clinical practitioners alike. One of the most powerful families of substances for probing active sites... more

Understanding and controlling carbohydrate processing enzymes (CPE) have been major issues and challenges for chemists, biochemists and clinical practitioners alike. One of the most powerful families of substances for probing active sites as well as allosteric interactions with CPEs are basic sugar analogues, in particular iminoalditols. This compound class presents a basic trivalent nitrogen instead of oxygen in the sugar ring as the common feature. Depending on the task, such molecules may show two faces, acting as powerful competitive inhibitors or as folding templates for the same CPE protein. When applied at sub-inhibitory concentration iminoalditols and derivatives thereof have become attractive as pharmacological chaperones for the treatment of lysosomal storage diseases. As such these structures can restore protein activity by assisting correct folding of mutant enzymes thus facilitating transportation to the lysosome and consequently substrate hydrolysis. This review surveys iminoalditol structures which have recently been investigated as potential pharmacological chaperones for the treatment of lysosomal storage diseases.

Accurate knowledge of the intracellular location of proteins is important for numerous areas of biomedical research including assessing fidelity of putative protein-protein interactions, modeling cellular processes at a system-wide level... more

Accurate knowledge of the intracellular location of proteins is important for numerous areas of biomedical research including assessing fidelity of putative protein-protein interactions, modeling cellular processes at a system-wide level and investigating metabolic and disease pathways. Many proteins have not been localized, or have been incompletely localized, partly because most studies do not account for entire subcellular distribution. Thus, proteins are frequently assigned to one organelle while a significant fraction may reside elsewhere. As a step towards a comprehensive cellular map, we used subcellular fractionation with classic balance sheet analysis and isobaric labeling/quantitative mass spectrometry to assign locations to >6000 rat liver proteins. We provide quantitative data and error estimates describing the distribution of each protein among the eight major cellular compartments: nucleus, mitochondria, lysosomes, peroxisomes, endoplasmic reticulum, Golgi, plasma m...