The use of cysteinyl peptides to effect portage transport of sulfhydryl-containing compounds in Escherichia coli.
We describe a method by which sulfhydryl compounds may be transported into Escherichia coli as the mixed disulfides with a cysteine residue of a di- or tripeptide. Transport occurs through the di- or oligopeptide transport systems, and it is suggested that subsequent release of the sulfhydryl compound occurs as a result of a disulfide exchange reaction with components of the sulfhydryl-rich cytoplasm. The free sulfhydryl compounds used here (2-mercaptopyridine and 4-[N-(2-mercaptoethyl)]aminopyridine-2,6-dicarboxylic acid) show weak growth-inhibitory properties in their own right, but disulfide linkage to a cysteinyl peptide results in a considerable enhancement (up to 2 orders of magnitude). This is the first example of the use of the peptide transport systems of E. coli to effect portage transport of a poorly permeant molecule by using attachment to the side chain of one of the amino acid residues of a peptide; all previous examples have involved the incorporation of amino acid analogues into the peptide backbone. The synthesis of cysteinyl peptides containing disulfide-linked 2-mercaptopyridine is described. Displacement of the 2-mercaptopyridine by sulfhydryl compounds of interest proceeds rapidly and quantitatively in aqueous alkaline solution to provide the required peptide disulfides.
D000631:Aminopyridines / Q000378:metabolism*; D001693:Biological Transport, Active / Q000187:drug effects; D003545:Cysteine / Q000031:analogs & derivatives* / Q000378:metabolism; D004926:Escherichia coli / Q000254:growth & development / Q000378:metabolism*; D009842:Oligopeptides / Q000494:pharmacology*; D011725:Pyridines / Q000378:metabolism
D000631:Aminopyridines; D009842:Oligopeptides; D011725:Pyridines; C040151:4-(N-(2-mercaptoethyl))aminopyridine-2,6-dicarboxylic acid; C040150:cysteine-2-mercaptopyridine; C029347:2-thiopyridine; D003545:Cysteine