Showing papers on "Aldose published in 2022"

Stereoselective Construction of Orthogonally Protected, N-O Interlinked Disaccharide Mimetics Using N-Substituted β-Aminooxy Donors.

Abstract: Orthogonally protected N-substituted β-aminooxy sugars can be stereoselectively synthesized from sugar epoxides and nitrones derived from aromatic aldehydes. Both the ether- and ester-protected sugar epoxides can be employed. The synthesized aminooxy sugars could be reacted with aldehyde bearing/free reducing sugars under the heating condition to afford N-O-linked 1,1-/1,5/1,6-disaccharide mimetics in a good yield.

Novel rhodanine based inhibitors of aldose reductase of non-acidic nature with p-hydroxybenzylidene functional group.

Abstract: Aldose reductase, the first enzyme of the polyol pathway represents a key drug target in therapy of diabetic complications. In this study a series of six novel rhodanine based inhibitors of aldose reductase was designed, synthesized, and tested for their ability to inhibit aldose reductase and for selectivity relative to structurally related aldehyde reductase. Aldose reductase inhibitory activities of the compounds were characterized by the IC50 values ranging from 2000 nM to 20 nM. The values of selectivity factors relative to aldehyde reductase were decreasing in the same array from 24 to 5. In silico docking into the inhibitor binding site of aldose reductase revealed a specific binding pattern of the compounds comprising interaction of the deprotonated 4-hydroxybenzylidene group with the anion-binding sub-pocket of aldose reductase, creating a strong H-bond and charge interactions. Predicted pH-distribution profiles of the novel compounds into octanol, supported by experimentally determined distribution ratios, favour drug uptake at the physiological pH, as a result of the presence of the low-acidic phenolic group, instead of the more acidic carboxymethyl functional group.

Covalent Adduct Formation in Methylthio-d-ribose-1-phosphate Isomerase: Reaction Intermediate or Artifact?

Abstract: Methylthio-d-ribose-1-phosphate (MTR1P) isomerase (MtnA) functions in the methionine salvage pathway by converting the cyclic aldose MTR1P to its open-chain ketose isomer methylthio-d-ribulose 1-phosphate (MTRu1P). What is particularly challenging for this enzyme is that the substrate's phosphate ester prevents facile equilibration to an aldehyde, which in other aldose-ketose isomerases is known to activate the α-hydrogen for proton or hydride transfer between adjacent carbons. We speculated that MtnA could use covalent catalysis via a phosphorylated residue to permit isomerization by one of the canonical mechanisms, followed by phosphoryl transfer back to form the product. In apparent support of this mechanism, [32P]MTR1P was found by SDS-PAGE and gel-filtration chromatography to radiolabel the enzyme. Susceptibility of this adduct to strongly acidic and basic pH and nucleophilic agents is consistent with an acyl phosphate. C160S and D240N, mutants of two conserved active-site residues, however, exhibited no difference in radiolabeling despite a reduction in activity of ∼107, leading to the conclusion that phosphorylation is unrelated to catalysis. Unexpectedly, prolonged incubations with C160S revealed up to 30% accumulation of radioactivity, which was identified by 31P and 13C NMR to be the result of a second adduct─a hemiketal formed between Ser160 and the carbonyl of MTRu1P. These results are interpreted as indirect support for a mechanism involving transfer of the proton from C-2 to C-1 by Cys160.

β-aldehyde ketones as dual inhibitors of aldose reductase and α-glucosidase with antioxidant properties

Abstract: In this study, a series of phenyl β-aldehyde ketones were designed and synthesized as novel dual inhibitors of aldose reductase (ALR2) and α-glucosidase. The results showed substantial inhibition of ALR2...