Antibacterial activity and uptake into Escherichia coli of backbone-modified analogues of small peptides.
Analogues of di- and tripeptides in which the peptide backbone is modified have been examined for antibacterial activity in vitro, and for uptake into Escherichia coli. Aminoxy and hydrazino types, in which the peptide linkage is replaced, respectively, by -CO-NHO- or -CO-NH-NH-, were active against E. coli, Staphylococcus aureus, and Salmonella dublin; retro, alpha-aza, tetrazole, and hydroxamic types were inactive. Highest potency against all three species was found in aminoxy analogues containing D-2-aminoxypropionic acid (D-OAla) residues, Ala-D-OAla being active at less than 1 mg 1-1. Uptake into E. coli was seen with all active types, but, with the exception of hydroxamic analogues not with the inactive types. Following uptake the toxic analogues were rapidly hydrolysed and the constituent amino acid residues underwent exodus. The substrate specificities of the peptide transport systems have been further defined on the basis of our results.
D000409:Alanine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects*; D001692:Biological Transport; D004151:Dipeptides / Q000378:metabolism / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects / Q000378:metabolism*
D004151:Dipeptides; C002956:alanylalanine; D000409:Alanine