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  • 1
    ISSN: 1573-904X
    Keywords: oligopeptide transporter ; structure-transport ; metabolism ; Caco-2 ; tripeptides ; cephalexin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. The purpose of this study was to determine the stereospecificity of the apical oligopeptide transporter(s) for the stereoisomers of Val-Val-Val and to determine whether the interaction of these molecules with this transporter(s) could be correlated with their cellular uptake and/or transepithelial transport. Methods. The interactions of these stereoisomers with this transporter(s) were evaluated by determining their ability to inhibit [3H]cephalexin uptake into Caco-2 cells. The metabolism of these stereoisomers was determined in a homogenate of Caco-2 cells and in the apical bathing solution over Caco-2 cell monolayers. The cellular uptake and transepithelial transport properties of these stereoisomers were studied using the Caco-2 cell monolayers. Results. The L-L-L tripeptide was totally degraded within 1 h in the Caco-2 cell homogenate and within 2 h when applied to the apical side of a Caco-2 cell monolayer. In contrast, 36.7 ± 1.3% and 69.7 ± 0.9% of L-Val-L-Val-D-Val remained after 2 h in the cell homogenate and in the apical bathing solution, respectively. The other six stereoisomers of Val-Val-Val were completely stable in the Caco-2 cell homogenate. Five of the stereoisomers (L-L-L, L-L-D, L-D-L, D-L-L, D-D-L) significantly inhibited the cellular uptake of [3H]cephalexin (91%, 62%, 14%, 45%, 16%, respectively). The other stereoisomers had no effect on the [3H]cephalexin uptake. When the cellular uptake of the stereoisomers was determined, the D-L-L and L-D-L tripeptides showed the highest intracellular concentrations (1.32 ± 0.25 and 0.62 ± 0.20 nmol/mg protein after a 2-h incubation, respectively). In contrast, the intracellular concentrations of the other stereoisomers were less than 0.1 nmol/mg protein. Moreover, the cellular uptake of the D-L-L and L-D-L tripeptides was inhibited by Gly-Pro by 82% and 68%, respectively, whereas Gly-Pro showed moderate to no inhibitory effect on the cellular uptake of the other stereoisomers. The permeability coefficients of the stereoisomers across the Caco-2 cell monolayers were very low (1.8 to 3.1 × 10−7 cm/sec) and almost identical. Gly-Pro had no effect on their transepithelial transport. Conclusions. These results suggest that the interaction of the Val-Val-Val stereoisomers with the apical oligopeptide transporter(s) could be a good predictor of their cellular uptake. However, since the major transepithelial transport mechanism of Val-Val-Val stereoisomers is passive diffusion via the paracellular route, the binding of these molecules to the oligopeptide transporter(s) is not a good predictor of their transepithelial transport. It appears that the stereochemical requirements for the transporter that mediates permeation of the peptide across the basolateral membrane may be different from the requirements for the apical transporter that mediates cellular uptake.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1573-904X
    Keywords: oligopeptide transporter ; structure-transport ; Caco-2 ; dipeptides ; carnosine ; cephalexin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. The purpose of this study was to determine whether the binding of the diastereomers of Val-Val to the apical oligopeptide transporter(s) could be correlated with their cellular uptake and transepithelial transport. Methods. The Caco-2 cell culture system was used for all experiments. The binding of the diastereomers of Val-Val was evaluated by determining their ability to inhibit [3H]cephalexin uptake. The stability of the diastereomers was determined in a homogenate of Caco-2 cells and in the apical bathing solution over Caco-2 cell monolayers. The cellular uptake and transepithelial transport properties of the individual diastereomers were studied using Caco-2 cell monolayers. Results. 10 mM concentrations of L-Val-L-Val, L-Val-D-Val, D-Val-L-Val and D-Val-D-Val inhibited cellular uptake of [3H]cephalexin (0.1 mM) by 92%, 37%, 70%, and 18%, respectively. When the cellular uptake of Val-Val diastereomers (1 mM) were evaluated, the intracellular concentrations of L-Val-D-Val and D-Val-L-Val were 15 and 50 times higher, respectively, than that of D-Val-D-Val. The cellular uptake of L-Val-D-Val and D-Val-L-Val was inhibited by Gly-Pro (10 mM) (〉95%), whereas Gly-Pro had no effect on the cellular uptake of D-Val-D-Val. L-Val-L-Val was not detected in the Caco-2 cells, probably due to its metabolic lability. When the transepithelial transport of the Val-Val diastereomers (1 mM) was determined, L-Val-D-Val, D-Val-L-Val and D-Val-D-Val transport rates were similar. The transepithelial transport of L-Val-D-Val and D-Val-L-Val was inhibited by Gly-Pro (10 mM) 36% and 30%, respectively, while Gly-Pro inhibited carnosine (1 mM) transepithelial transport by 65%. Gly-Pro had no effect on the transepithelial transport of D-Val-D-Val. Conclusions. These results suggest that the major transepithelial transport route of L-Val-D-Val, D-Val-L-Val and D-Val-D-Val is passive diffusion via the paracellular route. The binding of Val-Val diastereomers to the oligopeptide transporter(s) is a good predictor of their cellular uptake, however, the binding is not a good predictor of their transepithelial transport. It appears that the stereochemical requirements for the transporter that mediates efflux of the peptide across the basolateral membrane may be different from the requirements for the apical transporter that mediates cellular uptake.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1573-904X
    Keywords: oligopeptide transporter ; structure-transport ; Caco-2 ; dipeptides ; cephalexin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Hoboken, NJ : Wiley-Blackwell
    AIChE Journal 9 (1963), S. 338-342 
    ISSN: 0001-1541
    Keywords: Chemistry ; Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Additional Material: 7 Ill.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Stamford, Conn. [u.a.] : Wiley-Blackwell
    Polymer Engineering and Science 17 (1977), S. 613-621 
    ISSN: 0032-3888
    Keywords: Chemistry ; Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: ESR spin-probe values of glass temperatures are reported for a series of di-, tri-, and radial block copolymers. With one exception, in which the hard phase is poly(t-butylstyrene), the hard component is polystyrene (PS); the soft components include polybutadiene (PBD), polyisoprene (PI), hydrogenated PBD, hydrogenated PI, and poly(dimethyl siloxane) (PDMS). Tg's of the soft phase are in general agreement with those of the respective high molecular weight homopolymers; Tg's of the hard phase generally deviate widely from those of corresponding high molecular weight homopolymers. This deviation is interpreted in teens of a number of factors, including, the molecular weight of the hard phase, differences in solubility parameters for the two phases, percent of the hard phase present, and the presence of crystallinity. Comparison of Tg's determined by ESR with Tg's from dynamic mechanical methods on S-B-S triblocks of similar composition demonstrates that the ESR method is measuring the Tg of the interpliase and hence, in principle, its composition.
    Additional Material: 9 Ill.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Brookfield, Conn. : Wiley-Blackwell
    Journal of Vinyl and Additive Technology 12 (1990), S. 99-104 
    ISSN: 0193-7197
    Keywords: Chemistry ; Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Glass fiber reinforced PVC has several distinctive and useful properties. Its tensile strength can be twice that of unreinforced PVC. Excellent coupling of the glass fibers to the PVC matrix is required for good retention of tensile strength when exposed to warm water, Its modulus can be twice that of unreinforced PVC and equal to that of wood. PVC's high load carrying capability is not significantly increased to higher temperatures by adding glass fibers as judged by its 264 psi heat deflection temperature. However, by changing the polymeric matrix, glass reinforced vinyl with an increased HDT of 86°C has been produced for higher use temperature. The coefficient of linear thermal expansion of PVC can be cut in half by the addition of glass fibers and has a coefficient equal to that of aluminum. Glass fiber reinforced PVC has exceptionally good resistance to crack propagation and resists shattering as judged by sawing, punching, stapling, and hammering. When properly formulated for weathering resistance, glass fiber reinforced PVC has good color retention, impact retention, and outstanding dimensional stability. As for all glass fiber reinforced plastics, processing equipment must be built for high abrasion resistance for long economical manufacturing runs.
    Additional Material: 11 Ill.
    Type of Medium: Electronic Resource
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