The azidonitration of tri-<i>O</i>-acetyl-<scp>D</scp>-galactal

Lemieux, R. U.; Ratcliffe, R. M.

doi:10.1139/v79-203

Cited by 654 publications

(248 citation statements)

References 16 publications

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“…Indeed, even a remote effect of para-substituents of the benzoate groups on the reaction time was established (entries [12][13][14], and again, the unprotected 3-position afforded some oxidative byproduct (entry 11).…”

Section: Synthesis Of Glycalsmentioning

confidence: 99%

Remarkable Oxidation Stability of Glycals: Excellent Substrates for Cerium(IV)-Mediated Radical Reactions

et al. 2008

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Abstract:The remarkable stability of glycals under oxidative conditions becomes apparent by their redox data in solution, computed HOMO energies, and behavior on the addition of electrophilic radicals generated in the presence of cerium(IV) ammonium nitrate. Oxidation potentials up to 2.03 V vs ferrocene were obtained, which are exceptionally high for cyclic enol ethers but correlate nicely with the reaction times of the radical reactions. Protecting groups have a strong influence on the oxidation stability and HOMO energies of glycals as E ox is shifted from O-silyl over O-benzyl to O-acetyl by more than 500 mV. Interestingly, this effect must be transmitted through σ-bonds, even up to the para-position of a benzoate group, as verified by a wide variation of remote substituents in the carbohydrate. Favorable interactions of the σ*-orbital of the adjacent C-O bond with the HOMO of the double bond are proposed as a mechanistic rationale, which might be important for the redox behavior of other allylic systems. Finally, donors and acceptors in the 1-position exert the strongest influence on the oxidation stability, shifting the potentials by almost 1 V and resulting in different follow-up reactions of the cerium(IV)-mediated additions of malonates. It is the remarkable oxidation stability of glycals that makes them valuable building blocks in carbohydrate chemistry.

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Section: Synthesis Of Glycalsmentioning

confidence: 99%

Remarkable Oxidation Stability of Glycals: Excellent Substrates for Cerium(IV)-Mediated Radical Reactions

et al. 2008

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“…The affected homozygotes with Schindler disease had levels of a-GalNAc activity that were less than 1% of normal in various sources as assayed with the recently synthesized substrate, 4-methylumbelliferyl-a-N-acetylgalactosaminide (4MU-a-GalNAc) (2,7). Their parents had intermediate levels of activity consistent with being obligate heterozygotes for this autosomal recessive disorder.…”

Section: Introductionmentioning

confidence: 97%

Schindler disease: the molecular lesion in the alpha-N-acetylgalactosaminidase gene that causes an infantile neuroaxonal dystrophy.

Wang

Schindler²,

Desnick³

1990

J. Clin. Invest.

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Schindler disease is a recently recognized infantile neuroaxonal dystrophy resulting from the deficient activity of the lysosomal hydrolase, a-N-acetylgalctosaminidase (a-GalNAc). The recent isolation and expression of the full-length cDNA encoding a-GalNAc facilitated the identification of the molecular lesions in the affected brothers from family D, the first cases described with this autosomal recessive disease. Southern and Northern hybridization analyses of DNA and RNA from the affected homozygotes revealed a grossly normal aGalNAc gene structure and normal transcript sizes and amounts. Therefore, the a-GalNAc transcript from an affected homozygote was reverse-transcribed, amplified by the polymerase chain reaction (PCR), and sequenced. A single G to A transition at nucleotide 973 was detected in multiple subclones containing the PCR products. This point mutation resulted in a glutamic acid to lysine substitution in residue 325 (E325K) of the a-GalNAc polypeptide. The base substitution was confirmed by dot blot hybridization analyses of PCR-amplified genomic DNA from family members with allele-specific oligonucleotides. Furthermore, transient expression of an a-GalNAc construct containing the E325K mutation resulted in the expression of an immunoreactive polypeptide which had no detectable a-GalNAc activity. (J. Clin. Invest. 1990Invest. .86:1752Invest. -1756

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“…The peptide with an unnatural ␤-GalNAc at Ser-135 was denoted S135-␤-GalNAc. Fmoc-Ser(Ac 3 -␣-DGalNH Ac)-OH, Fmoc-Ser(Ac 3 -␤-D-GlcNH Ac)-OH and Fmoc-Ser(Ac 3 -␤-D-GalNHAc)-OH were prepared by modification of literature procedures (15)(16)(17)(18).…”

mentioning

confidence: 99%

One O-linked sugar can affect the coil-to-β structural transition of the prion peptide

Chen

Lin

Chang

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

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It has been known that the structural transition from PrP C to PrP Sc leads to the prion formation. This putative conformational change challenges the central dogma of the protein folding theory-''one sequence, one structure.'' Generally, scientists believe that there must be either a posttranslational modification or environmental factors involved in this event. However, all of the efforts to solve the mystery of the PrP C to PrP Sc transition have ended in vain so far. Here we provide evidence linking O-linked glycosylation to the structural transition based on prion peptide studies. We find that the O-linked ␣-GalNAc at Ser-135 suppresses the formation of amyloid fibril formation of the prion peptide at physiological salt concentrations, whereas the peptide with the same sugar at Ser-132 shows the opposite effect. Moreover, this effect is sugar specific. Replacing ␣-GalNAc with ␤-GlcNAc does not yield the same effect.T he prion protein (PrP, 254 aa for hamster PrP) has been found to be associated with the prion infectivity. The normal product of the prion gene is expressed as a glycophosphatidyl inositol-anchored glycoprotein on the outer cell membrane (1-3). The solution NMR structure of recombinant syrian hamster prion protein rPrP(90-231) was determined in 1997 (4). The secondary structure consists of three ␣-helices (144-153, 172-194, 200-227) interdispersed between two short ␤-strands (129)(130)(131)(161)(162)(163); the N terminus (90-111) is largely unstructured ( Fig. 1). A posttranslational process that converts the cellular prion protein (PrP C ) to the abnormal, insoluble, pathogenic isoform (PrP Sc ) has been implicated in the prion formation during the development of prion diseases.CD spectroscopy and Fourier transform infrared spectroscopy studies have indicated that approximately half of the ␣-helical and coiled structure in PrP C is transformed into ␤-sheet in PrP Sc (5). However, the thermodynamics of the ␣-to-␤ transition, including the factors that influence it, remain unknown. PrP C has a high turnover rate in vivo. This high turnover makes the purification of PrP C extremely difficult (6). The low yield of purified PrP C from animal brains or low level of expression in mammalian cells as well as the insolubility of PrP Sc have remained a bottleneck in prion research. It has been difficult to discern whether there are chemical modifications in PrP C that are absent in PrP Sc or vice versa. Although Edman sequencing data suggest that the amino acid sequence of PrP Sc is identical with the translational product of the prion gene (7), we cannot rule out the possibility of low levels of unidentified chemical modifications in PrP C or PrP Sc as the culprit of the medical malady. To date, the search for differential modifications between PrP C and PrP Sc has focused on the two N-linked glycosylation sites at N181 and N197. However, based on the results of tunicamycin treatment, an N-linked glycosylation inhibitor (8), as well as experiments on the expression of unglycosylated mutated prion prot...

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The azidonitration of tri-O-acetyl-D-galactal

Cited by 654 publications

References 16 publications

Remarkable Oxidation Stability of Glycals: Excellent Substrates for Cerium(IV)-Mediated Radical Reactions

Remarkable Oxidation Stability of Glycals: Excellent Substrates for Cerium(IV)-Mediated Radical Reactions

Schindler disease: the molecular lesion in the alpha-N-acetylgalactosaminidase gene that causes an infantile neuroaxonal dystrophy.

One O-linked sugar can affect the coil-to-β structural transition of the prion peptide

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