Gramicidines

Nevertheless, the technique suffers from a severe time scale problem -the trajectories are computed for (at most) a few nanoseconds. This is far too short compared to times required for many processes in biophysics. For example, the ii to T conformational transition in hemoglobin lasts tens of microseconds [1], and the typical time for ion migration through the gramicidin channel is hundreds of nanoseconds. This limits (of course) our ability to make a meaningful comparison to experiments, using MD. 

Staphylococcal a-hemolysin is another widely studied pore-forming toxin. It is used by infectious bacteria to perforate host animal cells by a mechanism that is distinct from that of gramicidin. Several aspects of the stmcture and function of this heptameric protein complex have been smdied. 

Antibiotics. The genes involved in the synthesis of a variety of antibiotics have been isolated (34,35). These include antibiotics such as erythromycin, streptomycin, and also peptide antibiotics such as gramicidin and tyrocidin. Characterization of these gene products facUitates the design of novel antibiotics. In addition, overexpression of some of these gene products is also expected to improve the yield of the antibiotic (34,35). 

In 1939 the isolation of a mixture of microbial products named tyrotbricin from a soil bacillus was described. Further investigation showed this material to be a mixture of gramicidin and tyrocidine. In rapid succession the isolation of actinomycin (1940), streptothricin (1942), streptomycin (1943), and neomycin (1949), produced by Streptomjces were reported and in 1942 the word antibiotic was introduced. Chloramphenicol, the first of the so-called broad spectmm antibiotics having a wide range of antimicrobial activity, was discovered in 1947. Aureomycin, the first member of the commercially important tetracycline antibiotics, was discovered in 1948. 

Most polymyxin B sold for human use in the United States is in dermatological, otic, and ophthalmic preparations that usually contain one or more other spectmm extending antibacterials such as bacitracin, neomycin sulfate [1404-04-2], C23H4gNg023, linear gramicidin, oxytetracycline [79-57-2],... 

Although tyrothricia is too toxic for parenteral therapy, it was formerly sold in the United States as oral lo2enges. Modem tyrothricin formulations are composed of 70—80% tyrocidines and 30—20% linear gramicidins. Tyrocidines are not as active as linear gramicidins and are too toxic for any therapeutic use by themselves. The bactericidal linear gramicidins are used in the United States solely as an ophthalmic solution in combination with polymyxin B sulfate and neomycin sulfate. The linear gramicidin is used in this aqueous product as a substitute for bacitracin, which lacks stabiUty under such conditions. 

Tyrocidine [8011-61-8] is a mixture of three closely related components. Tyrocidine studies on mechanism of action (98), biosynthesis on multien2yme complexes (93,99,100), and chemistry (101) are available, and tyrothricin production is discussed (102). Although the mechanism of action of linear gramicidins has been well researched, such work on tyrocidine is more limited it appears that tyrocidine damages membranes (103,104). 

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