Portage transport of sulfanilamide and sulfanilic acid.
Sulfanilic acid, in contrast to sulfanilamide, has poor in vitro antibacterial activity. Paradoxically, it has been shown to be a more effective inhibitor than sulfanilamide of dihydropteroic acid synthase. In order to circumvent the presumed permeability barrier to sulfanilic acid, advantage was taken of the technique of portage transport. Derivatives of the compound were prepared in which it was linked via its primary amino group to the alpha-carbon of glycine residues in di- and tripeptides. L-Alanyl-L-alanyl-L-2-[(4-sulfophenyl)amino]glycine proved to be 207 times more potent than sulfanilic acid and 8 times more active than either sulfanilamide or L-alanyl-L-alanyl-L-2-[[4-(aminosulfonyl)-phenyl]amino]glycine when tested against Escherichia coli. These findings confirm that the weak in vitro activity of sulfanilic acid is due to its limited ability to penetrate the bacterial membrane. They also emphasize the ability of portage transport to reveal therapeutic capability that had been attenuated by poor drug permeation.
Hwang
S Y
SY
Department of Biochemical Sciences, Princeton University, Princeton, New Jersey 08544.
Berges
D A
DA
Taggart
J J
JJ
Gilvarg
C
C
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000378:metabolism; D001557:Benzenesulfonates / Q000138:chemical synthesis*; D001692:Biological Transport; D055598:Chemical Phenomena; D002621:Chemistry; D004094:Dihydropteroate Synthase / Q000037:antagonists & inhibitors; D004151:Dipeptides / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects; D009842:Oligopeptides / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013424:Sulfanilamides / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D013425:Sulfanilic Acids / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D001557:Benzenesulfonates; D004151:Dipeptides; D009842:Oligopeptides; D013424:Sulfanilamides; D013425:Sulfanilic Acids; D004094:Dihydropteroate Synthase