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VB Lang P Langguth C Ottiger H Wunderli-Allenspach D Rognan B Rothen-Rutishauser JC Perriard S Lang J Biber HP Merkle 《Canadian Metallurgical Quarterly》1997,86(7):846-853
Due to the low effective permeabilities of peptides at many absorption sites, their structure-permeation relations are of high interest. In this work structure-permeation relations of Met-enkephalin analogues are presented using confluent Caco-2 cells as an in vitro permeation model. Four model peptides (Met-enkephalin, [D-Ala2]Met-enkephalin, [D-Ala2]Met-enkephalinamide, and metkephamid) were tested in terms of permeability, lipophilicity, charge, and molecular size. Permeability coefficients (P(eff)) across Caco-2 cells were low, 3.3 x 10(-8) to 9.5 x 10(-8) cm s-1, and were similar to typical paracellular markers. No correlation of permeability and the log(apparent octanol/buffer partition coefficient) was observed. A 40-fold increase of the permeability of metkephamid in the presence of 10 mM EDTA suggested a significant contribution of paracellular transport. Independent support for this conclusion was obtained by visualizing the pathway of the fluorescein isocyanate isomer I 1-metkephamid by confocal laser scanning microscopy (CLSM). The fluorophore-labeled peptide was observed in the intercallular space only. Metkephamid permeabilities were found to be direction-specific. Permeabilities from basolateral to apical (b-to-a) were significantly higher (ca. 4-fold) than in the opposite (a-to-b) direction. The addition of verapamil equalized the permeabilities in the a-to-b and b-to-a directions, suggesting the involvement of a P-glycoprotein-mediated secretion mechanism. Similar observations were obtained with [D-Ala2]Met-enkephalinamide, but not with Met-enkephalin and [D-Ala2]Met-enkephalin. In contrast to the other analogues, metkephamid and [D-Ala2]Met-enkephalinamide are positively charged at neutral pH, as demonstrated by their isoelectric points (pl = 8.6 for [D-Ala2]Met-enkephalinamide and metkephamid and 5.3 for [D-Ala2]Met-enkephalin and Met-enkephalin). The data is in agreement with the literature showing that most compounds secreted by the P-glycoprotein transporter carry a positive charge. 相似文献
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Is there a direct relationship between oral astringency and human salivary protein binding? 总被引:1,自引:0,他引:1
For decades, it is believed that astringency is due to the polyphenol-induced complexation of proline-rich salivary proteins
in the oral cavity. In order to compare for the first time the human sensory threshold concentrations and the salivary protein
binding activity of a series of astringent stimuli, human saliva protein was incubated for 5 min at 37 °C in the presence
of astringent food-derived compounds and, after micro-centrifugation, the amount of the target molecules in the supernatant
was quantitatively determined by HPLC-UV/Vis. Significant protein binding was observed for (−)-epigallocatechin-3-gallate,
(−)-gallocatechin-3-gallate, (+)-gallocatechin, and (−)-catechin-3-gallate, all of which containing at least one galloyl moiety
in the molecule and exhibiting rather high sensory thresholds of more than 200 μmol/L. In comparison, (+)-catechin and procyanidin
B2, both lacking in any galloyl function, showed only comparatively low binding activity and, most interestingly, quercetin-3-O-α-l-rhamnopyranosyl-(1 → 6)-β-d-glucopyranoside and 3-carboxymethyl-indole-1-N-β-d-glucopyranoside did not show any protein binding at all, although the later N- and O-glycosides exhibited extraordinarily low sensory threshold concentrations of less than 0.001 and 0.0003 μmol/L, respectively.
The data give some first evidence that the quantity of the non-bound, “free” astringent stimulus in the saliva liquid might
be more closely related to the sensory perception of astringency than the amount complexed or precipitated by proteins. It
is therefore questionable as to whether oral perception of astringency is related to the complexation and/or precipitation
of salivary proteins. 相似文献
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Herzog K. Schulte E. Atmanand M. A. Schwarz W. 《Automation Science and Engineering, IEEE Transactions on》2007,4(2):282-286
Tracked vehicles capable of locomotion in the deep sea are used for manganese nodule mining. This requires specific technical solutions in various respects. Locomotion in the soft sea bed is one of them. For the Crawler to safely maneuver, an automatic drive mode with slip control of the driving tracks is essential. Based on experimental studies at IKS, University of Siegen, slip control for the NIOT-IKS mining machine has been developed and implemented. The experimental setup for the development of the slip control along with the logic of the automatic driving mode is described. The system is critically discussed and the test results and future work are briefly outlined. Note to Practitioners-The work is carried out as part of the polymetallic nodule mining program of the Government of India. The technique of slip control is a specific requirement for a tracked vehicle used in the deep sea. Slip is common in many vehicles-tracked and otherwise. Examples are steam engines in the early days and ordinary cars while negotiating slush or snow/ice and dozers working in soft soil. While these are manually controlled by drivers who have firsthand knowledge of the environmental conditions, in the case of a mining machine in deep sea, it has to be completely automatic and, hence, is challenging. The knowledge generated in this work could be effectively used by practitioners in other related areas of automobile engineering for updating their expertise. Also, similar techniques may be used for maneuvering vehicles sent to other planets 相似文献
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