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Bioorg Med Chem Lett ; 59: 128545, 2022 03 01.
Article in English | MEDLINE | ID: mdl-35032607

ABSTRACT

An investigation into the effect of modified ß-lysines on the growth rates of eubacterial cells is reported. It is shown that the effects observed are due to the post translational modification of Elongation Factor P (EFP) with these compounds catalysed by PoxA. PoxA was found to be remarkably promiscuous, which allowed the activity of a wide range of exogenous ß-lysines to be examined. Two chain-elongated ß-lysine derivatives which differ in aminoalkyl chain length by only 2 carbon units exhibited opposing biological activities - one promoting growth and the other retarding it. Both compounds were shown to operate through modification of EFP.


Subject(s)
Anti-Bacterial Agents/pharmacology , Deoxyribonucleases/metabolism , Drug Design , Escherichia coli Proteins/metabolism , Escherichia coli/drug effects , Lysine/analogs & derivatives , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Escherichia coli/cytology , Escherichia coli/metabolism , Lysine/chemical synthesis , Lysine/chemistry , Lysine/pharmacology , Microbial Sensitivity Tests , Molecular Structure , Protein Processing, Post-Translational , Structure-Activity Relationship
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