Structure-Activity Study on the Kasugamycin Family

Abstract

Minosaminomycin (MSM), which is structurally related to kasugamycin (KSM), is active against mycobacteria but not against Gram negative bacteria. In vivo studies showed that MSM inhibits protein synthesis in mycobacteria. MSM, at 2×10⁻⁷M, also inhibits f₂ RNA-directed protein synthesis in an E. coli cell-free system by 50%. This inhibition is 100 times stronger than that caused by KSM in the same system. Like KSM, MSM preferentially inhibits the initiation process of protein synthesis. No increase in miscoding is observed in the presence of MSM. KG-8, a chemical derivative of KSM, is 10 times more inhibitory to the growth of E. coli than KSM. However, in the in vitro protein synthesizing system, KG-8 is not as inhibitory as KSM. These discrepancies between in vivo and in vitro activities may be ascribed to a difference in permeability, since E. coli cells with modified permeability show altered sensitivity to MSM. There is no indication that MSM is inactivated in E. coli cells. Based on these findings, the structure essential for binding to ribosomes and for permeation are discussed.