Mode streptomycin

The biochemical mode of action of the aminoglycosides as antibacterials has long been a topic of great interest. Early experiments carried out soon after the introduction of streptomycin suggested a variety of modes of action, but these conclusions were based largely on symptomatic analyses of antibiotic-treated bacterial cultures. One important experiment done in 1948 showed that streptomycin blocks enzyme indnction in susceptible bacteria this was the closest that anyone came to identifying the mechanism of action at the time. 

Ramakrishnan and co-workers 3-A crystal structures of two different aminoglycosides (paromomycin and streptomycin) bound to the 30S subunit laid to rest much of the debate concerning the binding mode of aminoglycoside antibiotics. Paromomycin was found bound to the major groove of helix 44 (H44), confirming mutagenesis studies that had been carried out previously. ... 

There is presently underway a very considerable amount of bacteriological work having as its objective the elucidation of the mode of action of streptomycin. 

In the purposeful search that followed the demonstration of the clinical efficacy of penicillin, streptomycin was obtained from Streptomyces griseus in 1944, cultured from a heavily manured field, and also from a chicken s throat. Aminoglycosides resemble each other in their mode of action, and their pharmacokinetic, therapeutic and toxic properties. The main differences in usage reflect variation in their range of antibacterial activity crossresistance is variable. 

Photosensitive derivatives of streptomycin (nitroguaiacol derivatives) have also been prepared by modification of the streptose unit, to study the mode of action of the antibiotic [189]. 

Glycopeptide antibiotics have been found to be very effective chiral selectors in the enantiomeric separation of racemic pharmaceutical compounds. Vancomycin, ristocetin A, rifamycins, teicoplanin, kanamycin, streptomycin, and avoparcin have been added to the running buffer to obtain enantioseparation (161,203— 207). A few technical modifications, such as coated capillaries and separation conditions in the reverse polarity mode (as opposed to normal polarity mode, where the flow is from anode to cathode) were found to improve sensitivity and increase efficiency (116,208). 

R. E. W Hancock, Aminoglycoside uptake and mode of action—with special reference to streptomycin and gentamicin. I. Antagonists and mutants, J. Antimicrob. Chemother., 8 (1981) 249-276. 

In addition, analogous experiments were carried out with puromycin (0.03 milligram per milliliter, as dihydrochloride), under conditions of repression or physiological derepression. In this case, no effect on the differential rates of formation of the transaminase, argininosuccinase, or acetylornithinase was observed. These negative findings with puromycin, on the one hand, indicate that the results with the 30 S inhibitors streptomycin and tetracycline are not nonspecific consequences of ribosomal inhibition or lowered growth rate and, on the other hand, would seem to reflect the differences in mode of action between these two inhibitors and puromycin. (A review of the mode of action of ribosomal inhibitors has recently been prepared by Pestka [104].)... 

The total synthesis of kasugamycin in stereochemically pure form has been achieved, albeit in low yield in its biosynthesis, glycine-N has been shown to be incorporated into the unique carboxyformidoyl function of this inositol-glycoside. The chemistry and biochemical mode of action of streptomycin was reviewed. Analysis of concentration effects on the extent of misreading of RNA code words induced... 

The higher resolution studies of subunits have also revealed the mode of action of several antibiotics such as paromomycin, streptomycin, and spectinomycin, which modify the decoding function of the small subunit, and chloramphenicol, puromycin, and vernamycin, which affect peptide bond formation. 

Assay Technique. Serum levels of viomycin, under certain dosage schedules, run rather high. It may be indicated that preliminary dilution of serum samples should be made. The mode of performance and interpretation should parallel that used for streptomycin (Section IV,2). 

The mode of action of streptomycin was studied with subcellular systems for protein synthesis, programmed by synthetic polyribonucleotides, or by phagic messenger RNAs. 

Studies of laboratory-derived (single-step) resistant mutants have proved to be of considerable biochemical utility. For example, streptomycin-resistant mutants have an altered receptor site due to a change in a protein of the small ribosomal subunit, while erythromycin-resistant mutants have a change in a protein of the large ribosomal subunit 7. Altered RNA polymerases are found in mutants resistant to rifampicin and streptol-ydigin 9. Fusidic acid resistance occurs as a result of mutations which alter a factor required in protein synthesis O. Such forms of antibiotic resistance have been useful in determining the mode of action of the antibiotic and in studies of macromolecular structure and function. By contrast, in "natural" resistance, the resistance mechanism is, in most cases, unrelated to the biochemical mode of action of the drug. The antibiotics with known plasmid-determined resistance are listed in Table 2. 

The introduction of penicillin into medical practice in 1941, and of streptomycin, chloramphenicol, and the tetracyclines in the following 8 years, opened up a new vista in chemotherapy. Antibiotics were at first regarded with much awe, and a completely new mode of action was predicted for them. In the course of time, though, they have been found to use the established types of receptor. Those antibiotics like penicillin and cephalosporin which prevent the synthesis of bacterial cell-wall have turned out to have an enzyme for receptor (Section 12.i), and this is true of the simpler oxamycin (Section 9.4). Many other antibiotics act on DNA, preventing its replication or transcription such are adriamycin, actinomycin, mitomycin, and bleomycin (Section 4.0). Rifamycin, however, acts on the protein of DNA-primed RNA-polymerase. 

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