Effect of Leucomycins and Analogues on Binding [ ¹⁴ C]Erythromycin to Escherichia coli Ribosomes

Abstract

We examined the effect of leucomycins, leucomycin derivatives, and other 16-membered macrolides (tylosin, iiiddamycin, spiramycin I, and spiramycin m) on [14C]erythromycin binding to ribosomes. Results of these studies enabled determination of the association and dissociation constants for the binding of each 'of these compounds to Escherichia coli ribosomes. In addition, the binding of the leucomycins and the leucomycin derivatives to ribosomes in general correlated with their antimicrobial activity.We recently examined the effect of erythromycin and its derivatives on chloramphenicol and erythromycin binding to ribosomes from Escherichia coli (10,11 (8,9). [14Clchloramphenicol binding to ribosomes was determined in 0.05-ml reaction mixtures (Fig 2). Each reaction mixture for determination of

Binding of (3H)tetrahydroleucomycin A3 to Escherichia coli ribosomes and the effect of 3"-O-acyl derivatives of leucomycins on the binding.

“…LMs were prepared in our laboratory7) and their 3"-acyl derivatives were synthesized according to SAKAKIBARA et al 3,9). Each compound was dissolved in 0.01 N HCl to make a stock solution of 10 mm.…”

“…PESTKA et al 3) and OMURA et al 4) studied the structure-activity relationship of leucomycins (LMs), the representative of 16-membered macrolides, by comparison of their antimicrobial activities with the affinities to ribosomes that were determined by competition with [14C]erythromycin in binding to Escherichia coli ribosomes.5) In general, the binding of LMs and their derivatives to ribosomes correlates with their antimicrobial activities against Gram-positive bacteria. However, where a discrepancy between antimicrobial activity and affinity to ribosomes exists, other factors such as cellular permeability or modification of the macrolide may be responsible.…”

Structure-activity relations among the O-acyl derivatives of leucomycin. Correlation of minimal inhibitory concentrations with binding to Escherichia coli ribosomes

“…We have studied the relationship between structure and microbial activity of 16-membered ring macrolide antibiotics, chiefly leucomycin and its derivatives.1,2 It has been speculated that the presence of the aldehyde group on the lactone ring and the dimethylamino group on the mycaminose moiety may be essential for antimicrobial activity.2, 3 The combination of antimicrobial and cell-free assays permits direct evaluation of such hypotheses.…”

“…The ability to inhibit erythromycin binding in general paralleled the antibacterial activity of these derivatives. 3,7,8 However, where discrepancies between antibacterial activity and binding to ribosomes exist, other factors such as cellular permeability or modification of the antibiotic may be particularly relevant. 3,7,8 In this paper, we describe the synthesis of acylated derivatives of leucomycin V. In addition, their antimicrobial activities (MIC) and their binding to ribosomes were evaluated.…”

Book Reviews

“…10 The concentration of each derivative which produced 50% inhibition of [14C]erythromycin binding to ribosomes was determined as described in previous reports. 3,7 For the last few years, the interrelations between the central nervous and endocrine systems have been intensely studied, and much progress has been made. Evidence is rapidly accumulating that the hormones derived from the brain (pituitary and hypothalamic peptides) and from the outer endocrine glands can exert direct brain effects, which may have behavioral consequences, entirely independent of their endocrine effects.…”