Aniline: A Catalyst for Sialic Acid Detection

Division of Translational Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390-9185, USA.
ChemBioChem (Impact Factor: 3.09). 09/2009; 10(13):2147-50. DOI: 10.1002/cbic.200900401
Source: PubMed
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    • "Aβ immunostained cortical amyloid plaques (red, 6E10, Fig. 5A,B), and biocytin hydrazide tagged protein carbonyls in amyloid plaques (green, Fig. 5A, and Fig. 5B, Biocytin). Transimination catalysis of this reaction with aniline [51] [52], visually resulted in more labeling of protein carbonyls within amyloid plaque and cells (Fig. 5A and B, Biocytin versus Biocytin + aniline). Thus, these results indicate that aldehyde and ketone modified proteins, or other oxidatively modified proteins are detected with this reagent in amyloid plaques [50,57–60]. "
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    ABSTRACT: Oxidative damage and amyloid-β (Aβ) protein misfolding are prominent features of Alzheimer's disease (AD). In vitro studies indicated a direct linkage between these two features, where lipid oxidation products augmented Aβ misfolding. We tested this linkage further, mimicking specific conditions present in amyloid plaques. In vitro lipid oxidation and lipid modification of Aβ were thus performed with elevated levels of copper or physiological levels of calcium. These in vitro experiments were then confirmed by in vivo immunohistochemical and chemical tagging of oxidative damage in brains from the PSAPP mouse model of AD. Our in vitro findings indicate that: 1) high levels of copper prevent lipid oxidation; 2) physiological concentrations of calcium reduce 4 hydroxy-2-nonenal (HNE) modification of Aβ; and 3) anti-Aβ and HNE antibody epitopes are differentially masked. In vivo we demonstrated increased lipid oxidation around plaques but 4) a lack of immunological colocalization of HNE-adducts with Aβ. Thus, the lack of colocalization of Aβ and HNE-adduct immunostaining is most likely due to a combination of metals inhibiting HNE modification of Aβ, quenching lipid oxidation and a masking of HNE-Aβ histopathology. However, other forms of oxidative damage colocalize with Aβ in plaques, as demonstrated using a chemical method for identifying oxidative damage. Additionally, these findings suggest that HNE modification of Aβ may affect therapeutic antibodies targeting the amino terminal of Aβ and that metals effect on lipid oxidation and lipid modification of Aβ could raise concerns on emerging anti-AD treatments with metal chelators.
    Journal of Alzheimer's disease: JAD 01/2010; 22(2):593-607. DOI:10.3233/JAD-2010-100960 · 4.15 Impact Factor
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    ABSTRACT: The recent development of metabolic oligosaccharide engineering combined with bioorthogonal reactions is providing unique opportunities to detect, image, and isolate glycoconjugates of living cells, tissues, and model organisms. In this methodology, exogenously-supplied non-natural sugars are fed to cells and employed by the biosynthetic machinery for the biosynthesis of neoglycoconjugates. In this way, reactive functional groups such as ketones, azides, and thiols have been incorporated into sialic acid, galactosamine, glucosamine, and fucose moieties of glycoconjugates. A range of bioorthogonal reactions have been described that functionalize the chemical 'tags' for imaging, isolation, and drug delivery.
    Carbohydrate Chemistry 01/2010; 36:152-167. DOI:10.1039/9781849730891-00152
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    ABSTRACT: The size of information that can be stored in nucleic acids, proteins, and carbohydrates was calculated. The number of hexamers for peptides is 64,000,000 (20(6)) and seems to be impressive in comparison with 4,096 (4(6)) hexanucleotides, but the number of isomers of hexasaccharides is 1.44 × 10(15). Carbohydrates are therefore the best high-density coding system. This language has been named glycocode resp. sugar code. In comparison with peptide dendrimers, the amount of information carried by glycopeptide dendrimers or glycodendrimers is therefore much higher. This is reflected by the variability of structures and functions (activities). This review is about the broad area of peptide and glycopeptide dendrimers. The dendrimeric state and physicochemical properties and general consequences are described, together with a cluster effect. The impact of cluster effect to biological, chemical, and physical properties is discussed. Synthesis of dendrimers by convergent and divergent approaches, "Lego" chemistry, ligation strategies, and click chemistry is given with many examples. Purification and characterization of dendrimers by chromatographic methods, electromigration methods, and mass spectrometry are briefly mentioned. Different types of dendrimers with cyclic core, i.e. RAFTs, TASPs and analogous cyclic structures, carbopeptides, carboproteins, octopus glycosides, inositol-based dendrimers, cyclodextrins, calix[4]arenes, resorcarenes, cavitands, and porphyrins are given. Dendrimers can be used for creation of libraries, catalysts, and solubilizing agents. Biocompatibility and toxicity of dendrimers is discussed, as well as their applications in nanoscience, nanotechnology, drug delivery, and gene delivery. Carbohydrate interactions of glycopeptide dendrimers (bacteria, viruses, and cancer) are described. Examples of dendrimers as anti-prion agents are given. Dendrimers represent a fast developing area which partly overlaps with nanoparticles and nanotechnologies.
    Amino Acids 08/2010; 40(2):301-70. DOI:10.1007/s00726-010-0707-z · 3.29 Impact Factor
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