Use of 4‐methylumbelliferyl‐6‐sulpho‐2‐acetamido‐2‐deoxy‐β‐<scp>D</scp>‐glucopyranoside for prenatal diagnosis of tay‐sachs disease using chorionic villi

Grebner, Eugene E.; Wenger, David A.

doi:10.1002/pd.1970070608

Cited by 11 publications

(4 citation statements)

References 6 publications

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“…On the other hand, sulfated flavonoids seem to have an important role in copigmentation; due to their increased water solubility, they form stable molecular complexes with polyphenolic pigments, such as anthocyanins, thus contributing to a strong intensification of the natural coloration . These photochemical properties could be of value in bioimaging techniques; for instant, several sulfated coumarins are already in use as substrates for fluorometric assays . Some studies indicate that sulfated flavonoids also play a role in the plant growth regulation, by bonding to the naphthylphtalamic acid receptor blocking the efflux inhibition of auxins …”

Section: Introduction: Nature As An Inspirationmentioning

confidence: 99%

Emerging Sulfated Flavonoids and other Polyphenols as Drugs: Nature as an Inspiration

2013

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Nature uses sulfation of endogenous and exogenous molecules mainly to avoid potential toxicity. The growing importance of natural sulfated molecules, as modulators of a number of physiological and pathological processes, has inspired the synthesis of non-natural sulfated scaffolds. Until the 1990s, the synthesis of sulfated small molecules was almost restricted to derivatives of flavonoids and aimed mainly at structure elucidation and plant biosynthesis studies. Currently, the synthesis of this type of compounds concerns structurally diverse scaffolds and is aimed at the development of potential drugs and/or exploitation of the biological effects of sulfated metabolites. Some important hit compounds are emerging from sulfated flavonoids and other polyphenols mainly as anticoagulant and antiviral agents. When compared with polymeric macromolecules such as heparins, sulfated small molecules could be of value in therapeutics due to their hydrophobic nature that can contribute to improve the bioavailability. This review highlights the synthetic approaches that were applied to obtain monosulfated or polysulfated phenolic small molecules and compiles the diverse biological activities already reported for this type of derivatives. Toxicity and pharmacokinetic parameters of this emerging class of derivatives will also be considered, emphasizing their value for therapeutic applications.

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Section: Introduction: Nature As An Inspirationmentioning

confidence: 99%

Emerging Sulfated Flavonoids and other Polyphenols as Drugs: Nature as an Inspiration

2013

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“…Peripheral leukocytes and plasma were analyzed for total β‐hexosaminidase (Hex) activity (including both type A and type B) using 4‐methylumbelliferyl‐β‐D‐N‐acetyl‐glucosaminide (4MU‐GlcNAc, 2.5 mM) and for Hex‐A activity only using 4‐methylumbelliferyl‐2‐acetamido‐2‐deoxy‐6‐sulfo‐β‐D‐glucopyranoside (4MU‐GlcNAcS, 2.5 mM) . Substrate hydrolysis was measured by fluorometric assay with an excitation wavelength of 365 nm and an emission wavelength 450 nm with a Bio‐Rad VersaFluor™ fluorometer .…”

Section: Methodsmentioning

confidence: 99%

“…Peripheral leukocytes and plasma were analyzed for total b-hexosaminidase (Hex) activity (including both type A and type B) using 4methylumbelliferyl-b-D-N-acetyl-glucosaminide (4MU-GlcNAc, e 2.5 mM) 12 and for Hex-A activity only using 4-methylumbelliferyl-2-acetamido-2-deoxy-6-sulfo-b-D-glucopyranoside (4MU-GlcNAcS, f 2.5 mM). 13…”

Section: Biochemical Analysismentioning

confidence: 99%

Canine GM2‐Gangliosidosis Sandhoff Disease Associated with a 3‐Base Pair Deletion in the HEXB Gene

Wang

Henthorn

Galban

et al. 2017

Veterinary Internal Medicne

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Background GM2‐gangliosidosis is a fatal neurodegenerative lysosomal storage disease (LSD) caused by deficiency of either β‐hexosaminidase A (Hex‐A) and β‐hexosaminidase B (Hex‐B) together, or the GM2 activator protein. Clinical signs can be variable and are not pathognomonic for the specific, causal deficiency.ObjectivesTo characterize the phenotype and genotype of GM2‐gangliosidosis disease in an affected dog.AnimalsOne affected Shiba Inu and a clinically healthy dog.MethodsClinical and neurologic evaluation, brain magnetic resonance imaging (MRI), assays of lysosomal enzyme activities, and sequencing of all coding regions of HEXA, HEXB, and GM2A genes.ResultsA 14‐month‐old, female Shiba Inu presented with clinical signs resembling GM2‐gangliosidosis in humans and GM1‐gangliosidosis in the Shiba Inu. Magnetic resonance imaging (MRI) of the dog's brain indicated neurodegenerative disease, and evaluation of cerebrospinal fluid (CSF) identified storage granules in leukocytes. Lysosomal enzyme assays of plasma and leukocytes showed deficiencies of Hex‐A and Hex‐B activities in both tissues. Genetic analysis identified a homozygous, 3‐base pair deletion in the HEXB gene (c.618‐620delCCT).Conclusions and Clinical ImportanceClinical, biochemical, and molecular features are characterized in a Shiba Inu with GM2‐gangliosidosis. The deletion of 3 adjacent base pairs in HEXB predicts the loss of a leucine residue at amino acid position 207 (p.Leu207del) supporting the hypothesis that GM2‐gangliosidosis seen in this dog is the Sandhoff type. Because GM1‐gangliosidosis also exists in this breed with almost identical clinical signs, genetic testing for both GM1‐ and GM2‐gangliosidosis should be considered to make a definitive diagnosis.

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“…Detection of c~-L-iduronidase activity directly in tissues was carried out as described (Grebner and Wenger, 1987). The bottom of a petri dish (60 x 15 ram) was covered with filter paper moistened with formate buffer, pH 3.5.…”

Section: Methodsmentioning

confidence: 99%

Use of 4‐trifluoromethylumbelliferyl‐α‐l‐iduronide as a new substrate for detection of α‐l‐iduronidase deficiency in human tissues and for rapid prenatal diagnosis of Hurler disease

Tsvetkova

Карпова

Voznyi

et al. 1990

J of Inher Metab Disea

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Results are presented of alpha-L-iduronidase assays in the leukocytes of normal individuals, patients with Hurler disease and heterozygous carriers. The assays were carried out using 4-methylumbelliferyl-alpha-L-iduronide and 4-trifluoromethylumbelliferyl-alpha-L-iduronide as substrates. It was shown that 4-trifluoromethylumbelliferyl-alpha-L-iduronide, along with the commonly used 4-methylumbelliferyl-alpha-L-iduronide, can serve as a specific substrate for alpha-L-iduronidase and is therefore suitable for demonstrating the enzyme deficiency in patients with Hurler disease, as well as the decrease of enzyme activity in heterozygous disease carriers. Using the two substrates a prenatal diagnosis of Hurler disease in a fetus was made on the basis of the lack of enzyme activity in amniotic fluid cell cultures. The diagnosis was confirmed by the results of alpha-L-iduronidase activity assay in fetal liver and kidney. It was found that 4-trifluoromethylumbelliferyl-alpha-L-iduronide is highly efficient for the rapid detection of alpha-L-iduronidase deficiency directly in pieces of tissues and in placenta, which is important for the prenatal diagnosis of Hurler disease.

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Use of 4‐methylumbelliferyl‐6‐sulpho‐2‐acetamido‐2‐deoxy‐β‐D‐glucopyranoside for prenatal diagnosis of tay‐sachs disease using chorionic villi

Cited by 11 publications

References 6 publications

Emerging Sulfated Flavonoids and other Polyphenols as Drugs: Nature as an Inspiration

Emerging Sulfated Flavonoids and other Polyphenols as Drugs: Nature as an Inspiration

Canine GM2‐Gangliosidosis Sandhoff Disease Associated with a 3‐Base Pair Deletion in the HEXB Gene

Use of 4‐trifluoromethylumbelliferyl‐α‐l‐iduronide as a new substrate for detection of α‐l‐iduronidase deficiency in human tissues and for rapid prenatal diagnosis of Hurler disease

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