Portage of various compounds into bacteria by attachment to glycine residues in peptides

Abstract

Synthetic di- and oligopeptides are described that contain nucleophilic moieties attached to the α carbon of a glycine residue. These peptides are accepted by the peptide transport system of Escherichia coli (and other microorganisms) and are capable of being hydrolyzed by intracellular peptidases. After liberation of its amino group the α-substituted glycine is chemically unstable (although it is stable in peptide form) and decomposes, releasing the nucleophilic moiety. Thus, the combined result of peptide transport and peptidase action is the intracellular release of the nucleophile. Peptides containing glycine residues α-substituted with thiophenol, aniline, or phenol are used as models for this type of peptide-assisted entry and their metabolism by E. coli is described. Peptides of this type have broad applicability to the study of microbial physiology and the development of an additional class of antimicrobial agents.