Roflamycoin--a new channel-forming antibiotic.
Ion permeability of lipid bilayers was studied in the presence of a new antifungal pentaene antibiotic, roflamycoin, the structure of which differs considerably from that of the well-known polyene channel-former amphotericin B. Both of them, however, show the property of increasing the membrane permeability only in the case of sterol-containing membrane when added on both its sides. The conductance is strongly dependent on the concentration of the antibiotic in the solutions and of sterol in the membrane. Unlike the amphotericin B channels, roflamycoin channels are potential-dependent and have short lifetime (approx. 1 s) and high conductance (approx. 100 ps in 1 M KCl), which increases linearly with the salt concentration and is not blocked by the familiar blockers of amphotericin B channels. The two antibiotics seem to have a common mechanism of channel formation, viz. the formation starts from two semi-pores assembled in the opposite monolayers from several molecules of the antibiotic and sterol. However, the inner diameter of the roflamycoin channel is larger because of the different antibiotic-to-sterol ratio in the channel aggregate. It is believed that the difference in the ratio is due to the presence of the methyl group in the polyene chain of roflamycoin, and the considerable difference in lifetimes of the two types of channels depends on the terminal groups of the antibiotics.
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Grigorjev
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Schlegel
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Thrum
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Ermishkin
D000666:Amphotericin B / Q000494:pharmacology; D000935:Antifungal Agents / Q000494:pharmacology*; D004553:Electric Conductivity; D007473:Ion Channels / Q000187:drug effects*; D007700:Kinetics; D008051:Lipid Bilayers / Q000378:metabolism*; D008433:Mathematics; D008564:Membrane Potentials; D011090:Polyenes / Q000494:pharmacology; D013997:Time Factors
D000935:Antifungal Agents; D007473:Ion Channels; D008051:Lipid Bilayers; D011090:Polyenes; C030620:flavomycoin; D000666:Amphotericin B