STREPTOMYCYLAMINES: DIFFERENCE IN ACTIVITY AND MODE OF ACTION BETWEEN SHORT-CHAIN AND LONG-CHAIN DERIVATIVES

Abstract

A homologue series of aliphatic streptomycylamines (SM-amines) have been prepared and tested in vitro (binding to 70S ribosomes) and in vivo (MIC). The short-chain SM-amines act as streptomycin (SM) but are less active than SM. They are inactive towards a SM-resistant Escherichia coli, our strain 042. The long-chain SM-amines are active both towards our sensitive and resistant E. coli, our strains 079 and 042. Their activities are not pH-dependent in contrast to that of SM. However, the higher homologues of the aliphatic amines (C₁₀-C₁₆) are considerably active per se although two to four times less than the corresponding SM-amines. Further, the amines do not compete with the SM-amine for the binding to the ribosomal particles. The binding affinities of these long-chain SM-amines to ribosomes are considerably smaller than that of SM. The binding is however specific as a typical isotope dilution curve can be obtained. We conclude that the long-chain SM-amines have a mode of action different from that of SM.