Dataset Information

O-Acetyl Side-Chains in Monosaccharides: Redundant NMR Spin-Couplings and Statistical Models for Acetate Ester Conformational Analysis.

ABSTRACT: ?- and ?-d-glucopyranose monoacetates 1-3 were prepared with selective 13C enrichment in the O-acetyl side-chain, and ensembles of 13C-1H and 13C-13C NMR spin-couplings (J-couplings) were measured involving the labeled carbons. Density functional theory (DFT) was applied to a set of model structures to determine which J-couplings are sensitive to rotation of the ester bond ?. Eight J-couplings (1JCC, 2JCH, 2JCC, 3JCH, and 3JCC) were found to be sensitive to ?, and four equations were parametrized to allow quantitative interpretations of experimental J-values. Inspection of J-coupling ensembles in 1-3 showed that O-acetyl side-chain conformation depends on molecular context, with flanking groups playing a dominant role in determining the properties of ? in solution. To quantify these effects, ensembles of J-couplings containing four values were used to determine the precision and accuracy of several 2-parameter statistical models of rotamer distributions across ? in 1-3. The statistical method used to generate these models has been encoded in a newly developed program, MA'AT, which is available for public use. These models were compared to O-acetyl side-chain behavior observed in a representative sample of crystal structures, and in molecular dynamics (MD) simulations of O-acetylated model structures. While the functional form of the model had little effect on the precision of the calculated mean of ? in 1-3, platykurtic models were found to give more precise estimates of the width of the distribution about the mean (expressed as circular standard deviations). Validation of these 2-parameter models to interpret ensembles of redundant J-couplings using the O-acetyl system as a test case enables future extension of the approach to other flexible elements in saccharides, such as glycosidic linkage conformation.

SUBMITTER: Turney T

PROVIDER: S-EPMC5556682 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

O-Acetyl Side-Chains in Monosaccharides: Redundant NMR Spin-Couplings and Statistical Models for Acetate Ester Conformational Analysis.

Turney Toby T Pan Qingfeng Q Sernau Luke L Carmichael Ian I Zhang Wenhui W Wang Xiaocong X Woods Robert J RJ Serianni Anthony S AS

The journal of physical chemistry. B 20161221 1

α- and β-d-glucopyranose monoacetates 1-3 were prepared with selective 13C enrichment in the O-acetyl side-chain, and ensembles of 13C-1H and 13C-13C NMR spin-couplings (J-couplings) were measured involving the labeled carbons. Density functional theory (DFT) was applied to a set of model structures to determine which J-couplings are sensitive to rotation of the ester bond θ. Eight J-couplings (1JCC, 2JC ...[more]

PMID: 28001427

Similar Datasets

Project description:A new type of block copolymer micelles for pH-triggered delivery of poorly water-soluble anticancer drugs has been synthesized and characterized. The micelles were formed by the self-assembly of an amphiphilic diblock copolymer consisting of a hydrophilic poly(ethylene glycol) (PEG) block and a hydrophobic polymethacrylate block (PEYM) bearing acid-labile ortho ester side-chains. The diblock copolymer was synthesized by atom transfer radical polymerization (ATRP) from a PEG macro-initiator to obtain well-defined polymer chain-length. The PEG-b-PEYM micelles assumed a stable core-shell structure in aqueous buffer at physiological pH with a low critical micelle concentration as determined by proton NMR and pyrene fluorescence spectroscopy. The hydrolysis of the ortho ester side-chain at physiological pH was minimal yet much accelerated at mildly acidic pHs. Doxorubicin (Dox) was successfully loaded into the micelles at pH 7.4 and was released at a much higher rate in response to slight acidification to pH 5. Interestingly, the release of Dox at pH 5 followed apparently a biphasic profile, consisting of an initial fast phase of several hours followed by a sustained release period of several days. Dox loaded in the micelles was rapidly taken up by human glioma (T98G) cells in vitro, accumulating in the endolysosome and subsequently in the nucleus in a few hours, in contrast to the very low uptake of free drug at the same dose. The dose-dependent cytotoxicity of the Dox-loaded micelles was determined by the MTT assay and compared with that of the free Dox. While the empty micelles themselves were not toxic, the IC(50) values of the Dox-loaded micelles were approximately ten-times (by 24h) and three-times (by 48h) lower than the free drug. The much enhanced potency in killing the multi-drug-resistant human glioma cells by Dox loaded in the micelles could be attributed to high intracellular drug concentration and the subsequent pH-triggered drug release. These results establish the PEG-b-PEYM block copolymer with acid-labile ortho ester side-chains as a novel and effective pH-responsive nano-carrier for enhancing the delivery of drugs to cancer cells.

Dataset Information

O-Acetyl Side-Chains in Monosaccharides: Redundant NMR Spin-Couplings and Statistical Models for Acetate Ester Conformational Analysis.

Publications

O-Acetyl Side-Chains in Monosaccharides: Redundant NMR Spin-Couplings and Statistical Models for Acetate Ester Conformational Analysis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets