80876-59-1

Usage

Uses

Used in Pharmaceutical Industry:
L-Idaric-1,4-lactone is used as an inhibitor of α-L-idosidase for its potential therapeutic applications in treating lysosomal storage disorders, such as I-cell disease and mucopolysaccharidoses, by modulating the activity of the enzyme and improving the clearance of accumulated substrates.
Used in Research Applications:
L-Idaric-1,4-lactone serves as a valuable research tool in biochemical and cell biology studies, where it can be employed to investigate the role of α-L-idosidase in various biological processes and its potential as a target for drug development.

InChI:InChI=1/C6H8O7/c7-1-2(8)6(12)13-4(1)3(9)5(10)11/h1-4,7-9H,(H,10,11)/t1-,2-,3?,4-/m0/s1

Upstream product

• 527-00-4 allo-mucic acid 
• 526-99-8 meso-galactaric acid 
• 7437-69-6 2,4:3,5-di-O-methylene-L-idaric acid 
• 4539-77-9 2,4:3,5-di-O-methylene-D-glucaric acid dimethyl ester 
• 685-73-4 D-galacturonic acid 

Downstream Products

• 47173-55-7 galactaric acid mono-(N'-phenyl-hydrazide) 

Relevant academic research and scientific papers

Crystal structure of uronate dehydrogenase from Agrobacterium tumefaciens

Uronate dehydrogenase from Agrobacterium tumefaciens (AtUdh) belongs to the short-chain dehydrogenase/reductase superfamily and catalyzes the oxidation of D-galacturonic acid and D-glucuronic acid with NAD+ as a cofactor. We have determined the crystal structures of an apo-form of AtUdh, a ternary form in complex with NADH and product (substrate-soaked structure), and an inactive Y136A mutant in complex with NAD+. The crystal structures suggest AtUdh to be a homohexamer, which has also been observed to be the major form in solution. The monomer contains a Rossmann fold, essential for nucleotide binding and a common feature of the short-chain dehydrogenase/reductase family enzymes. The ternary complex structure reveals a product, D-galactaro-1,5-lactone, which is bound above the nicotinamide ring. This product rearranges in solution to D-galactaro-1,4-lactone as verified by mass spectrometry analysis, which agrees with our previous NMR study. The crystal structure of the mutant with the catalytic residue Tyr-136 substituted with alanine shows changes in the position of Ile-74 and Ser-75. This probably altered the binding of the nicotinamide end of NAD+, which was not visible in the electron density map. The structures presented provide novel insights into cofactor and substrate binding and the reaction mechanism of AtUdh. This information can be applied to the design of efficient microbial conversion of D-galacturonic acid-based waste materials.

SYNTHESIS OF L-IDARO-1,4-LACTONE, AN INHIBITOR OF α-L-IDOSID-URONASE

L-Idaro-1,4-lactone was synthesized by two different, published methods: (1) epimerization of monopotassium D-glucarate by refluxing in aqueous barium hydroxide, and (2) oxidation of L-iditol by heating in dilute nitric acid.The lactone, formed by heat dehydration from aqueous solution at low pH, was purified by paper chromatography, and quantitated by gas-liquid chromatography using inositol as the internal standard.The monolactone inhibited human, seminal-fluid α-L-idosiduronase activity, with either phenyl or 4-methylumbelliferyl α-L-idosiduronic acid as the substrate, to the same degree as D-glucaro-1,4-lactone inhibits α-D-glucosiduranose.