The effect of chloramphenicol analogs on protein biosynthesis in a cell-freeEscherichia coli B system

Telesnina, G. N.; Новикова, М. А.; Zhdanov, G.L.; Kolosov, M. N.; Shemyakin, M. M.

doi:10.1007/bf02142155

Cited by 7 publications

(4 citation statements)

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“…vitro activity: the deacylated chloramphenicol base has only ~6 per cent of the activity of chloramphenicol in a poly UC (1:1) system which polymerizes phenylalanine (Coutsogeorgopoulos, 1966). At 4 x 10-4 M, the dibromoacetyl, monochloroacetyl, trichloroacetyl, acetyl and dichlorocrotonyl derivatives were as active as chloramphenicol itself in an incorporation system without added messenger RNA (Telesnina et al, 1967). The monobromo-and monoiodoacetyl derivatives of chloramphenicollhind irreversibly to the ribosomal site of action of the antibiotic, probably by reacting with a strategically placed amino acid functional group; therefore, these derivatives inhibit model protein synthesis irreversibly (Bald, Erdmann and Pongs, 1972).…”

Section: Concentration Of Chloramphenicolmentioning

confidence: 97%

“…However, while strong electronegativity and, also, lipophilic properties of the acyl substituents are requirements for bacterial growth inhibition in addition to restrictions of the size of this substituent, no such requirements appear to exist for the inhibition of model protein synthesis in vitro. For five acyl derivatives of chloramphenicol, Telesnina et al (1967) found superior in vitro activities on model protein synthesis when-compared to bacterial growt~inhibition and concluded that the most important function of the acyl substituent is "in the penetration of the antibiotic into the bacterial cell. "…”

Section: Comparison Of In Vivo and In Vitro Structure-activity Rumentioning

confidence: 98%

“…Para-substituents were -SCH3' -S02CH3i -S02NH2 and -NHCOCH3. At concentrations between 3.13 x 10-6 M and 4 x 10-'1 M, compounds inhibited a variety of amino acid polymerization systems with (Vazquez, 1966) or without (Telesnina, Novikova, Zhdanov, Kolosov and Shemiakin, 1967) added messengers. The p-amino reduction product of chloramphenicol is devoid of activity (Coutsogeorgopoulos, 1966).…”

Section: Concentration Of Chloramphenicolmentioning

confidence: 98%

“…to the binding of chloramphenicol to its receptor site, in contrast to other properties which are requirements for the penetration of the drug into bacterial cells. The only work which has compared in vivo and in vitro effects of chloramphenicol derivatives side by side is that:of Telesnina et al (1967) whose stated objective was to bring "the structure-activity studyclOser to the molecular level." I.…”

Section: Comparison Of In Vivo and In Vitro Structure-activity Rumentioning

confidence: 99%

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A Structural Model of the Chloramphenicol Receptor Site

Hahn¹,

Gund²

1975

Drug Receptor Interactions in Antimicrobial Chemotherapy

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I . I NTRODUCTI ONHaving a relatively simple chemical structure, chloramphenicol became the first antibiotic to be synthesized by organic-chemical methods (Controulis, Rebstock and Crooks, 1949). A large number of chloramphenicol derivatives was subsequently prepared. Kolosov, Shemiakin, Khokhlov and Gurevich tabulated, in 1961, more than 500 such compounds, and the total number of known chloramphenicol derivatives is, by now, much greater.For many of these substances, data on their growth-inhibitory potencies for bacteria have been reported. Also, after it was recognized that chloramphenicol acts through specific inhibition of bacterial protein biosynthesis (Hahn and Wisseman, 1951; Gale and Folkes, 1953; Wisseman, Smadel, Hahn and Hopps, 1954) and cell-free model systems of protein synthesis were subsequently developed, chloramphenicol derivatives have been tested for inhibitions of such systems. Hence, the chloramphenicol series of compounds appears to be suited to the derivation of structure-activity relationships.The recent identification of a chloramphenicol binding protein which is a constituent of the 50s subunit of 70s ribosomes (Nierhaus and Nierhaus, 1973;Pongs, Bald and Erdmann, 1973) has renewed our interest in these structureactivity relationships and has encouraged us to analyze them with a view to deriving a structural model of a chloramphenicol receptor site which we infer to be located on the peptidyl transferase which is part of the 50s ribosomal subunit. II. STRUCTURE-ACTIVITY RELATIONSHIPS WHICH DETERMINE INHIBITION OF BACTERIAL GROWTHFirst systematic efforts to derive for chloramphenicol derivatives structureactivity rules for bacterial growth inhibition were made by Hahn (1955), Shemiakin, Kolosov, Levitov, Germanova, Karapetian, Shvetsov and Bamdas (1955, 1956) and Hahn, Hayes, Wisseman, Hopps and Smadel (1956). Both groups of workers arrived independently at the same conclusions; reviews of these conclusions represented the state of the art for several years (Kolosov et al., 1961;Hahn, 1967a). Both groups also called attention to the fact that data-on growth inhibitions by chloramphenicol derivatives had been obtained in many laboratories using varieties of methods and test organisms and could not be considered to be better than semi-quantitative approximations which did not lend themselves to the derivation of quantitative structure-activity relationships.

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Section: Concentration Of Chloramphenicolmentioning

confidence: 97%

Section: Comparison Of In Vivo and In Vitro Structure-activity Rumentioning

confidence: 98%

Section: Concentration Of Chloramphenicolmentioning

confidence: 98%

Section: Comparison Of In Vivo and In Vitro Structure-activity Rumentioning

confidence: 99%

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