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  • Title: [Effect of vitamin B1 structural analogue 3-decyloxycarbonylmethyl-4-methyl-5-(beta-hydroxyethyl) thiazole chloride on transmembrane current via ion channels formed by amphotericin B in bilayer lipid membrane].
    Author: Shaturs'kyĭ OIa, Romanenko OV, Himmel'reĭkh NH.
    Journal: Ukr Biokhim Zh (1999); 2009; 81(2):57-67. PubMed ID: 19873878.
    Abstract:
    The structural analogue of vitamin B1 (thiamine)-3-decyloxycarbonylmethyl-4-methyl-5-(beta-hydroxyethyl) thiazole chloride (DMHT) introduced from the cis-side of cholesterol-containing phospholipid bilayer membrane reversibly reduced the conductance induced by amphotericin B channels reconstituted from the same side of membrane. Introduction of DMHT (0.1 mM) from the cis-side of membrane blocked the amphotericin B-created conductance in symmetric solution of 100 mM KCI by 84 +/- 2%. The conductance of one-sided amphotericin B channels remained unaffected, when DMHT was introduced separately to the opposite trans-side of membrane. The kinetics of amphotericin B channels inhibition with DMHT showed no cooperativity allowing to expect that negatively charged ionogenic groups of these channels formed one DMHT binding site per channel as the slope of blocking rate determined in double-log coordinates was 1.5. Relatively high pK of binding with amphotericin B channels (5.13) suggests that this site provides high-affinity interaction with DMHT. The comparative analysis of inhibition kinetics with the other blockers of amphotericin B channels--tetraethylammonium and tetramethylammonium has proved that DMHT is a comparable though much more potent substitute for both tetraalkylammonia. Hence, the DMHT was proposed as a novel powerful blocker for cation-selective channels with the size of the pore ranging between 0.28 nm and 0.385 nm.
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