Isolation of reducing oligosaccharide chains from the chondroitin/dermatan sulfate-protein linkage region and preparation of analytical probes by fluorescent labeling with 2-aminobenzamide.
The glycosaminoglycan (GAG)-protein linkage regions of various proteoglycans share the common tetrasaccharide GlcA-Gal-Gal-Xyl-attached to Ser residues in the core proteins. In previous analysis we demonstrated unique modifications by epimerization, sulfation and phosphorylation of the component sugars. Here we developed a sensitive analytical method for the linkage region oligosaccharides to detect or monitor structural variations and changes. This will be useful for investigation of their biological roles, which are largely unknown, but they have been implicated in biosynthesis. A variety of linkage region-derived hexasaccharides was first prepared as reducing sugar chains from peptide chondroitin/dermatan sulfate of whale cartilage, shark cartilage, and bovine aorta by means of chondroitinase digestion in conjunction with beta-elimination in the absence of reducing reagents, but involving a mild alkali, 0.5 M LiOH, at 4 degrees C to prevent peeling reactions. The structures of these oligosaccharides were determined by the combination of HPLC, enzymatic digestion, matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry, and (1)H NMR spectroscopy, which revealed eleven different hexasaccharides including a novel structure, DeltaHexAalpha1-3GalNAcbeta1-4IdoAalpha1-3Gal(4-O-sulfate)beta1-3Galbeta1-4Xyl (DeltaHexA and IdoA represent unsaturated hexuronic acid and L-iduronic acid, respectively). These oligosaccharides were labeled with a fluorophore, 2-aminobenzamide, to prepare analytical probes using the recently developed procedure [Kinoshita and Sugahara (1999) Anal. Biochem. 269, 367-378]. The fluorophore-tagged hexasacharides of low picomoles were well separated by HPLC and successfully analyzed by MALDI-TOF mass spectrometry. The principle of the method should be applicable to the analysis of the linkage region oligosaccharides derived from heparin and heparan sulfate as well. (+info)
Stereoselective reactions. XXXIIII. Design and synthesis of chiral bidentate amines having a bulky group on the chiral carbon.
Based on the solution structures of chiral bidentate lithium amides ((R)-3a,b) having a phenyl group on the chiral carbon, chiral bidentate amines ((R)-5a,b-8a,b and (S)-9a,b) having a bulkier group instead of a phenyl group on the chiral carbon were designed and synthesized. (+info)
Self-assembly of a metal-ion-bound monolayer of trigonal connectors on mercury: an electrochemical Langmuir trough.
The adsorption of the trigonal connector, 1,3,5-tris[10-(3-ethylthiopropyl)dimethylsilyl-1,10-dicarba-closo-decaboran-1-yl] benzene (1), from acetonitrile/0.1 M LiClO(4) on the surface of mercury at potentials ranging from +0.3 to -1.4 V (vs. aqueous Ag/AgCl/1 M LiCl) was examined by voltammetry, Langmuir isotherms at controlled potentials, and impedance measurements. No adsorption is observed at potentials more negative than approximately -0.85 V. Physisorption is seen between approximately -0.85 and 0 V. At positive potentials, adsorbate-assisted anodic dissolution of mercury occurs and an organized surface layer is formed. Although the mercury cations are reduced at -0.10 V, the surface layer remains metastable to potentials as negative as -0.85 V. Its surface areas per molecule and per redox center are compatible with a regular structure with the connectors 1 woven into a hexagonal network by RR'S-->Hg(2)(2+)<--SRR' or RR'S-->Hg(2+)<--SRR' bridges. The structure is simulated closely by geometry optimization in the semiempirical AM1 approximation. (+info)
Asymmetric synthesis of a selective endothelin A receptor antagonist.
An asymmetric synthesis of a selective endothelin A receptor antagonist 1b is described. Asymmetric conjugate addition of aryllithium derived from 18 to the chiral oxazoline 17 followed by hydrolysis afforded 15 in 96% ee via purification as (S)-(-)-1-phenylethylamine salt. Pd(OAc)(2)/dppf (1,1'-bis(diphenylphosphino)ferrocene) catalyzed carbonylation followed by chemoselective addition of aryllithium derived from 23 which gave ketone 24. Diastereoselective reduction of the ketone with catecholborane followed by concomitant activation of the resulting alcohol and cyclization gave the late intermediate 26. Introduction of amino moiety on the pyridine ring by imidoyl rearrangement followed by deprotection and purification by crystallization furnished the enantiomerically pure target molecule 1b in 8% overall yield from 16. (+info)
A chiral ligand-mediated asymmetric addition of a lithium BHA ester enolate to an aldehyde.
The asymmetric reaction of a lithium enolate generated from a BHA (2, 6-di-tert-buty-4-methoxyphenyl) propanoate was allowed to react with benzaldehyde in the presence of a diether-type chiral ligand affording the corresponding anti-aldol product in a moderate enantioselectivity. A tetradentate ligand induced better enantioselectivity albeit relative loss of anti-selectivity. A variation of lithiating amide agent affected the selectivity, indicating involvement of an amine as a component of the mixed aggregate. Absolute configuration of some of the aldol products was determined by standard transformations. (+info)
Fern constituents: triterpenoids from Adiantum capillus-veneris.
Two new migrated hopane triterpenoids, viz. 4alpha-hydroxyfilican-3-one and fern-9(11)-en-12beta-ol, and olean-18-en-3-one and olean-12-en-3-one as the first example of oleanane compounds from Adiantum ferns were isolated along with many other known triterpenoids from Adiantum capillus-veneris of China and Egypt. Their structures were elucidated by spectroscopic analyses. (+info)
Early life stress changes concentrations of neuropeptide Y and corticotropin-releasing hormone in adult rat brain. Lithium treatment modifies these changes.
Experiences of early life stress are more prevalent among depressed patients than healthy controls. Neuropeptide Y (NPY) was suggested to play a role in the pathophysiology of depression. Consequently, we investigated in adult rats the effects of maternal deprivation for 3 h/day during postnatal days (PND) 2-14 and of dietary lithium during PND 50-83 on brain levels of NPY-like immunoreactivity (LI). Brain levels of corticotropin-releasing hormone (CRH) and serum corticosterone were also measured. Maternal deprivation reduced NPY-LI levels in the hippocampus and the striatum but increased NPY-LI and CRH-LI levels in the hypothalamus. Lithium treatment counteracted the effect of maternal deprivation in the hippocampus and striatum by increasing NPY-LI levels. In the hypothalamus, lithium tended to decrease CRH-LI but further increased levels of NPY-LI; it also increased serum corticosterone levels. The results suggest that early life stress has long-term effects on brain NPY with implications for the development of depression/vulnerability to stress, and that one therapeutic mechanism of action of lithium is to increase brain NPY. (+info)
Mood stabilisers plus risperidone or placebo in the treatment of acute mania. International, double-blind, randomised controlled trial.
BACKGROUND: Few double-blind trials have examined the efficacy of a combination of a mood stabiliser and an atypical antipsychotic in acute mania. AIMS: To determine the efficacy of risperidone in combination with a mood stabiliser in acute mania. METHOD: Patients taking a mood stabiliser were randomised to 3 weeks' treatment with risperidone (n=75) or placebo (n=76). RESULTS: Young Mania Rating Scale (YMRS) scores improved rapidly with significantly greater reductions at week 1 in the risperidone group compared with the placebo group. At end-point YMRS scores decreased by 14.5 and 10.3 points in the risperidone and placebo groups, respectively. Significant improvements v. placebo (P<0.05) were noted in the risperidone group on several other clinically meaningful measures. Additionally, a post hoc analysis excluding carbamazepine-treated patients (plasma concentrations of risperidone active moiety were 40% lower in this group) revealed significantly greater reductions (P=0.047) in YMRS scores in the risperidone group than in the placebo group. Incidence of adverse events was similar in both groups. CONCLUSIONS: Risperidone is superior to placebo when used in combination with lithium or divalproex in acute mania. (+info)