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  • 1
    Electronic Resource
    Electronic Resource
    The intrinsic Cl–conductance of mouse kidney cortex brush-border membrane vesicles is not related to CFTR (1997)
    Springer
    Pflügers Archiv 434 (1997), S. 575-580 
    Details
    ISSN: 1432-2013
    Keywords: Key words Brush-border ; Membrane vesicle ; Cystic fibrosis transmembrane regulator (cftr) ; Alternate Cl ; conductance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstracts  Brush-border membrane vesicles (BBMV) were prepared from whole Balb/c mice kidneys by a Mg2+ precipitation technique. The presence of an intrinsic Cl–conductance co-expressed with Na+/glucose cotransport was inferred by the anion dependence of [14C]glucose uptake and overshoot with inward Na+-anion gradients. In Na+-equilibrated conditions, an inside-negative membrane potential difference (p.d.) produced by an inward Cl–gradient alone was capable of driving intravesicular [14C]glucose accumulation. The apparent anion conductance had a selectivity of Br– = I– = Cl– 〉  F–〉〉 gluconate, was inhibited by 0.5 mM 5-nitro-2- (3-phenylpropylamino)-benzoic acid (NPPB) but was unaffected by 0.5 mM 4,4′-diisothiocyanatostilbene 2,2′-disulphonate (DIDS). BBMV were isolated from mice in which the CFTR gene had been disrupted by a termination mutation (–/–) and compared with normal litter mates (+/+) and heterozygotes (–/+)[18]. [14C]Glucose uptake in NaCl media was significantly greater than glucose uptake in Na gluconate media for all three genotypes measured at 20 s: for homozygous –/– animals [14C]glucose uptake was increased by 2.80 ± 0.53 fold in Cl–media compared to gluconate media, n = 6; for wild-type +/+, by 2.16 ± 0.53 fold, n = 8; and for heterozygous +/– animals, by 2.17 ± 0.45 fold, n = 8. The observation of a Cl–-dependent component in BBMV isolated from homozygous –/– mutant animals shows that the chloride conductance in these vesicles cannot be due to cftr expression.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004240050438
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  • 2
    Electronic Resource
    Electronic Resource
    Co-expression of an anion conductance pathway with Na+-glucose cotransport in rat renal brush-border membrane vesicles (1993)
    Springer
    Pflügers Archiv 423 (1993), S. 406-410 
    Details
    ISSN: 1432-2013
    Keywords: Brush border ; Membrane vesicle ; Cl− conductance ; Cystic fibrosis transmembrane regulator ; Na-glucose cotransport
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Brush-border membrane vesicles were prepared from superficial rat renal cortex by a Mg2+-precipitation technique. The initial (20 s) [14C]glucose uptake rate from solutions containing 100 mmol/l Na (salt) was found to be dependent upon the anion composition of the medium; in comparison to gluconate-containing medium (0.46±0.05 nmol/mg protein), Cl− accelerated the initial rate to 1.47±0.21 nmol/mg protein (n=4 preparations, ± SEM). This enhancement was reduced by 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB, 0.5 mmol/l), but was unaffected by 4,4′-diisothiocyanatostilbene 2,2′-disulphonate (DIDS, 0.5 mmol/l). When membrane vesicles were pre-equilibrated with 100 mmol/l K (salt) and 100 mmol/l mannitol and glucose uptake was measured from a solution containing 100 mmol/l Na gluconate and 100 mmol/l mannitol in the presence of 80 μmol/l valinomycin (to generate an outward K+ diffusion electrical p. d.), it was found that intravesicular KCl depressed the initial glucose uptake compared to K gluconate. NPPB (0.5 mmol/l) increased the initial glucose uptake with intravesicular KCl towards values seen in K gluconate vesicles. In conditions where the only driving force for glucose uptake was established by an inward anion gradient (Nao=Nai) it was found that inward Cl− gradients could drive uphill glucose transport and that this was sensitive to NPPB (0.5 mmol/l), but insensitive to DIDS. We conclude that a Cl− conductance co-exists with Na-cotransport in rat renal brush-border membrane vesicles prepared from superficial renal cortex and this may function to regulate the activity of electrogenic transport systems at this membrane.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00374934
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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    Total Synthesis of Oxazole- and Cyclopropane-Containing Epothilone A Analogues by the Olefin Metathesis Approach (1997)
    Weinheim : Wiley-Blackwell
    Chemistry - A European Journal 3 (1997), S. 1957-1970 
    Details
    ISSN: 0947-6539
    Keywords: epothilone ; oxazoles ; cyclopropanes ; metathesis ; total synthesis ; Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: For structure-activity relationship studies, two series of epothilone A (1) analogues have been designed and synthesized, one containing an oxazole moiety instead of the thiazole heterocycle and the other containing a spirocyclopropane moiety in place of the gem-dimethyl group at position C-4 (4,4-ethano-epothilones). The olefin metathesis strategy in solution was utilized for the chemical synthesis of these compounds starting with key building blocks 7-9 for the oxazole series (compounds 2, 14-18, 21-26) and building blocks 8, 30, and 31 for the 4,4-ethano series (compounds 3,39-43, 46-51). The convergent strategy towards the designed epothilone A series involved a) an aldol condensation reaction, b) an esterification reaction, c) an olefin metathesis reaction catalyzed by [RuCl2(=CHPh)-(PCy3)2], and d) epoxidation of the macrocycle double bond.
    Additional Material: 2 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/chem.19970031211
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    Paper (German National Licenses)
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  • 4
    Electronic Resource
    Electronic Resource
    Total Synthesis of Oxazole- and Cyclopropane-Containing Epothilone B Analogues by the Macrolactonization Approach (1997)
    Weinheim : Wiley-Blackwell
    Chemistry - A European Journal 3 (1997), S. 1971-1986 
    Details
    ISSN: 0947-6539
    Keywords: epothilone ; oxazoles ; cyclopropanes ; total synthesis ; macrolactonizations ; Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: In order to probe structure-activity relationships in the epothilone area, two series of epothilone B analogues have been designed and synthesized. The first series containing an oxazole moiety in place of a thiazole on the side chain was constructed by utilizing key intermediates 7-9 or 10, 12, and 13 (Scheme 1), whereas the second series containing an ethano group instead of the gem-dimethyl group at position 4 was synthesized from fragments 42 and 43. A Yamaguchi-type macrolactonization reaction was used to construct the macrocycle from a secoacid, which was assembled, in both cases, by means of a) an aldol reaction, b) an Enders alkylation, and c) a Wittig-type reaction. This convergent strategy provided access to oxazole analogues 2,4,29-32 and 4,4-ethano derivatives 3,40,60-63 for biological studies.
    Additional Material: 2 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/chem.19970031212
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    Paper (German National Licenses)
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