Biomedical subjects

U J Nilsson

Publications and source records attributed to U J Nilsson.

5 recordsLinked to original sources

PubMed2001

A study of the donor properties of sialyl phosphites having an auxiliary 3-(S)-phenylseleno group.

Two phosphite sialyl donors, each having an auxiliary 3-(S)-phenylseleno group, were prepared and evaluated. The phenylseleno group was introduced via a new mode of generating phenylselenenic acid ('PhSeOH'). Although the sialyl donors provided fair yields (32-76%) of the desired sialosides in glycosylations of the reactive acceptor 1,2;3,4-di-O-isopropylidene-alpha-D-galactopyranose, no sialylated products could be obtained with less reactive acceptors. The presence of a 5-N-acetylacetamido group on the phosphite sialyl donor did not appear to improve its sialylating capability. The weak C-Se bond, possibly in combination with a steric hindrance, which disfavors alpha-nitrilium ion formation, seem to explain the unsuccessful sialylations of the less reactive acceptors.

Gangliosides↗

PubMed2000

Solid-phase extraction for combinatorial libraries.

Solid-phase extraction (SPE) has during the last three years emerged as a convenient method for the purification of compound libraries prepared by solution synthesis. The widespread use of SPE in combinatorial chemistry can be explained by straightforward SPE method development facilitated by the availability of numerous commercial SPE resins. High-speed automated SPE is readily accomplished by taking advantage of commercial laboratory robot systems. The present review summarizes and discusses advancements made in the use of different SPE resins and molecule tagging techniques for optimization of ion-exchange, reversed-phase, normal-phase and fluorous-phase SPE in combinatorial chemistry.

Chromatography, Liquid↗

PubMed1999

Parallel solution synthesis of a "Carbohybrid" library designed to inhibit galactose-binding proteins.

Parallel solution S-alkylations of a 1-thio-beta-D-galactopyranoside derivative with Michael acceptors and alpha-chloroketones, followed by ketone reductions, reductive aminations, and acylations were developed to yield a library of 1-thio-beta-D-galactopyranosides carrying small and diverse polar-neutral, hydrophobic, aromatic, cationic, or anionic non-carbohydrate aglycon structures. Screening of the library against a panel of galactose recognizing plant lectins revealed microM inhibitors of toxin A of A. precatorius superior to the reference ligands lactose and N-acetyl lactosamine. Such small, monosaccharide based inhibitors are attractive lead-molecules for therapeutic development, since they are low-molecular, hydrolytically stable and more hydrophobic than natural oligosaccharides.

Calcium-Binding Proteins↗

PubMed1998

Solid-phase extraction on C18 silica as a purification strategy in the solution synthesis of a 1-thio-beta-D-galactopyranoside library.

A novel strategy for the purification of carbohydrate-based chemical libraries synthesized in solution was developed. Purification of reaction products was accomplished by means of solid-phase extraction enabled by protecting the 2-, 3-, 4-, and 6-hydroxyl groups of a galactose derivative as their hydrophobic O-laurates. The presence of multiple O-laurates allowed adsorption of reaction products onto C18 silica while reagents and by-products were washed away with MeOH. Products were quantitatively eluted with pentane. Purification of products using solid-phase extraction offers the combined advantages of solution synthesis (normal solution reactivity and ease of reaction monitoring) with those of solid-phase synthesis (facile product isolation permitting the use of large excesses of reagents). To demonstrate the utility of the hydrophobic recovery-procedure, tetra-O-lauroyl-beta-D-galactopyranose-1-thiol was subjected to high-yielding reactions with a panel of Michael-acceptors and an alpha-chloro ketone. The resulting ketone adducts were then either reduced to the alcohols or reductively aminated with a selection of amino acids to give 30 different 1-thio-beta-D-galactosides as mixtures of four diastereomers after removal of protecting groups. At each step, the product was separated from the reagents and their by-products by simple adsorption onto C18 silica, washing with MeOH and elution of product with pentane. After completion of the combinatorial chemistry sequence, the O-laurates were cleaved by methanolysis and the product methyl laurate in turn removed from the desired water-soluble products by C18 adsorption. Individual library members were thus conveniently produced on 10-30 mg scales at purity levels of > 90%. One of the 1-thio-beta-D-galactosides thus produced was found to be a competitive inhibitor of the beta-galactosidase from E. coli with Ki value of 1.7 microM.

Carbohydrate Conformation↗

PubMedDate not supplied

Immobilization of reducing sugars as toxin binding agents.

A simple and economical procedure for the attachment of reducing sugars to aminated solid supports has been developed. Reaction of the amino groups on the solid support with p-nitrophenyl chloroformate, followed by 1,6-hexanediamine, yields a chain-extended amine to which reducing sugars can be attached while remaining accessible to macromolecules. Immobilization of the reducing sugars involves a simple incubation followed by trapping of the resulting glycosylamine with acetic anhydride and recovery of the unreacted sugar by filtration. This technique was used to immobilize lactose and sialyllactose onto silylaminated Chromosorb P, producing solid supports that effectively neutralized the activity of cholera toxin from Vibrio cholerae and heat-labile enterotoxin of enterotoxigenic Escherichia coli. The general applicability of such solid supports for toxin neutralization was further demonstrated by immobilization of the enzymatically synthesized alpha Gal(1-3) beta Gal(1-4)Glc trisaccharide, which produced a support that efficiently neutralized toxin A of Clostridium difficile. The results from this study suggest that these solid supports have the potential to serve as inexpensive therapeutics for bacterial toxin-mediated diarrheal diseases.

Animals↗