27 research outputs found
Synthesis of a stable, storable and differentially protected acyclic precursor of D-amicetose and its conversion to 4-O-benzyl-protected D-amicetose
1851-1857Two carbon chain homolgation of enantiopure four carbon erythro configured iodo derivative 5 with N-methoxy-N-methyl-2-phenylsulfonylacetamide 6 affords for the first time a stable and storable precursor 3 of D-amicetose in the acyclic form, wherein the sensitive aldehyde is masked as a Weinreb amide. The differential protection in this acyclic derivative offers all the potential to exclusively arrive at the pyranose form of the target dideoxy-sugar
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Intramolecular arylation of a cyclic β-diketone using Mn(OAc)3 is applied for construction of the spirocyclic structure in Fredericamycin A
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Developmental regression and mitochondrial function in children with autism
BACKGROUND: Developmental regression (DR) occurs in about one-third of children with Autism Spectrum Disorder (ASD) yet it is poorly understood. Current evidence suggests that mitochondrial function in not normal in many children with ASD. However, the relationship between mitochondrial function and DR has not been well-studied in ASD.
METHODS: This cross-sectional study of 32 children, 2 to 8 years old with ASD, with (n = 11) and without (n = 12) DR, and non-ASD controls (n = 9) compared mitochondrial respiration and mtDNA damage and copy number between groups and their relation to standardized measures of ASD severity.
RESULTS: Individuals with ASD demonstrated lower ND1, ND4, and CYTB copy number (Ps \u3c 0.01) as compared to controls. Children with ASD and DR had higher maximal oxygen consumption rate (Ps \u3c 0.02), maximal respiratory capacity (P \u3c 0.05), and reserve capacity (P = 0.01) than those with ASD without DR. Coupling Efficiency and Maximal Respiratory Capacity were associated with disruptive behaviors but these relationships were different for those with and without DR. Higher ND1 copy number was associated with better behavior.
CONCLUSIONS: This study suggests that individuals with ASD and DR may represent a unique metabolic endophenotype with distinct abnormalities in respiratory function that may put their mitochondria in a state of vulnerability. This may allow physiological stress to trigger mitochondrial decompensation as is seen clinically as DR. Since mitochondrial function was found to be related to ASD symptoms, the mitochondria could be a potential target for novel therapeutics. Additionally, identifying those with vulnerable mitochondrial before DR could result in prevention of ASD
Weinreb amide based building blocks for convenient access to various synthetic targets
1749-1756N-Methoxy-N-methylamide, popularly known as the Weinreb amide (WA), has served as an excellent acylating agent for organolithium and/or organomagnesium reagents and a robust equivalent for an aldehyde group. The stability of the WA functionality, its ease of preparation, the scalability of its reactions and its predictable reactivity are the key features responsible for its prominent use in several synthetic endeavors by the chemists world-wide. The development of WA-based building blocks and synthetic equivalents for interesting synthons has been a long drawn pursuit initiated in nineties and through this mini-review accomplishments in this direction, with particular emphasis on the building blocks, developed recently in the last three years are summarized
Age-Dependent Properties of Acid & Alkaline DNases in Chick Brain
Acid and alkaline DNase activities in partially purified preparations from young and old chick brain were measured. The
specific activity of acid DNase from old brain was lower by about 50% than that of enzyme from young brain , whereas alkaline
DNase exhibited only marginal difference in activity of the two preparations . Study of various properties, viz. heat-stability
and effect of exogenous compounds like Mg=', Hgl', Zn=', PHM B , on these enzymes revealed that while acid DNase in old
brain is more susceptible to heat and heavy metal ion inhibition , alkaline DNase is devoid of any age-dependent variation in
its properties
Ceramide Inhibition of Mammalian Phospholipase D1 and D2 Activities Is Antagonized by Phosphatidylinositol 4,5-Bisphosphate †
Lipid Peroxidation-Derived Reactive Aldehydes Directly and Differentially Impair Spinal Cord and Brain Mitochondrial Function
Mitochondrial bioenergetic dysfunction in traumatic spinal cord and brain injury is associated with post-traumatic free radical–mediated oxidative damage to proteins and lipids. Lipid peroxidation by-products, such as 4-hydroxy-2-nonenal and acrolein, can form adducts with proteins and exacerbate the effects of direct free radical–induced protein oxidation. The aim of the present investigation was to determine and compare the direct contribution of 4-hydroxy-2-nonenal and acrolein to spinal cord and brain mitochondrial dysfunction. Ficoll gradient–isolated mitochondria from normal rat spinal cords and brains were treated with carefully selected doses of 4-hydroxy-2-nonenal or acrolein, followed by measurement of complex I– and complex II–driven respiratory rates. Both compounds were potent inhibitors of mitochondrial respiration in a dose-dependent manner. 4-Hydroxy-2-nonenal significantly compromised spinal cord mitochondrial respiration at a 0.1-μM concentration, whereas 10-fold greater concentrations produced a similar effect in brain. Acrolein was more potent than 4-hydroxy-2-nonenal, significantly decreasing spinal cord and brain mitochondrial respiration at 0.01 μM and 0.1 μM concentrations, respectively. The results of this study show that 4-hydroxy-2-nonenal and acrolein can directly and differentially impair spinal cord and brain mitochondrial function, and that the targets for the toxic effects of aldehydes appear to include pyruvate dehydrogenase and complex I–associated proteins. Furthermore, they suggest that protein modification by these lipid peroxidation products may directly contribute to post-traumatic mitochondrial damage, with spinal cord mitochondria showing a greater sensitivity than those in brain