PMID: 3758072Sep 15, 1986Paper

Aminoacylaminonucleoside inhibitors of protein synthesis. A new approach for evaluating their potency

European Journal of Biochemistry
D A TheocharisC Coutsogeorgopoulos

Abstract

In a model system derived from Escherichia coli, Ac[3H]Phe-puromycin is produced in a pseudo-first-order reaction between the preformed Ac[3H]Phe-tRNA-poly(U)-ribosome complex (complex C) and excess puromycin [Kalpaxis et al. Eur. J. Biochem. 154, 267, 1986]. Amicetin and gougerotin inhibit this reaction to various degrees depending on whether or not complex C is allowed to interact with the inhibitor (I) prior to the addition of puromycin (S). The kinetic analysis shows a phase where competitive inhibition can be observed provided that S and I are added simultaneously. After preincubating C with I, the inhibition becomes of the mixed non-competitive type. The Ki (the dissociation constant of the CI complex), calculated from the competitive plot, is 20.0 microM for amicetin and 15.0 microM for gougerotin. This inhibition constant (Ki) cannot distinguish amicetin from gougerotin. Its acceptance as a criterion of potency does not explain why after preincubation amicetin proves to be a stronger inhibitor than gougerotin. The determination of the apparent catalytic rate constants of peptidyltransferase at various inhibitor concentrations and the appropriate replotting of these rate constants distinguish amicetin from gougerotin. A ...Continue Reading

References

Jan 1, 1976·Progress in Nucleic Acid Research and Molecular Biology·S Pestka
Jan 15, 1986·European Journal of Biochemistry·D L KalpaxisC Coutsogeorgopoulos
Jun 9, 1972·Biochemical and Biophysical Research Communications·C CoutsogeorgopoulosJ T Miller
Jan 1, 1971·Annual Review of Microbiology·S Pestka
Dec 9, 1965·Biochimica Et Biophysica Acta·S R Casjens, A J Morris

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Citations

May 1, 1992·The International Journal of Biochemistry·D A Theocharis
Aug 1, 1992·The International Journal of Biochemistry·D A Theocharis, D Drainas
Apr 1, 1987·European Journal of Biochemistry·D DrainasC Coutsogeorgopoulos
Jun 30, 1992·Biochemistry·D A Theocharis, C Coutsogeorgopoulos
Feb 1, 1989·Analytical Biochemistry·D A Theocharis, C Coutsogeorgopoulos
Nov 1, 1992·Archives of Biochemistry and Biophysics·S Kallia-RaftopoulosC Coutsogeorgopoulos

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