Antibacterial halogenoacetyl derivatives of amino acids and simple peptides

Article abstract of DOI:10.1021/jm00221a015

The vital role of D-alanine and L-lysine in the peptidoglycan crosslinking process in the bacterial cell wall prompted preparation of various small peptides incorporating these amino acids. N-Iodoacetyl or -bromoacetyl derivatives of the peptides were then prepared in the hope that they would serve as active-site-directed irreversible inhibitors of cell wall transpeptidases. Certain of the halogenoacetyl dipeptide esters, but not the corresponding free acids, showed slight antistaphylococcal activity. Subsequent structural variation showed that inclusion of D-alanine or L-lysine was not necessary, since antibacterial activity was at least as good when the dipeptide unit was replaced by glycylglycine or by an ω-aminoalkanoic acid. It was concluded that the observed antibacterial activity was probably not due to specific inhibition of a cell wall transpeptidase.