Phosphinate, sulfonate, and sulfonamidate dipeptides as potential inhibitors of Escherichia coli aminopeptidase N.
In an effort to prepare novel inhibitors of bacterial aminopeptidase N (PepN), the phosphinate, propenylphosphinate, decylphosphinate, sulfonate, and sulfonamidate analogs of Ala-Ala were synthesized and tested as inhibitors. Phosphinate 1 was shown to inhibit PepN with a K(i) of 10microM, and propenylphosphinate 2 and decylphosphinate 3 inhibited PepN with a K(i) of ca. 1microM. Sulfonate and sulfonamidate analogs did not inhibit PepN.
Yang
Ke-Wu
KW
Department of Chemistry and Biochemistry, 160 Hughes Hall, Miami University, Oxford, OH 45056, USA.
Golich
Frank C
FC
Sigdel
Tara K
TK
Crowder
Michael W
MW
D000626:Aminopeptidases / Q000037:antagonists & inhibitors*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors*; D004151:Dipeptides / Q000737:chemistry*; D004926:Escherichia coli / Q000201:enzymology*; D010721:Phosphinic Acids / Q000737:chemistry / Q000494:pharmacology; D011480:Protease Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D013449:Sulfonamides / Q000737:chemistry / Q000494:pharmacology; D013451:Sulfonic Acids / Q000737:chemistry / Q000494:pharmacology
D001426:Bacterial Proteins; D004151:Dipeptides; D010721:Phosphinic Acids; D011480:Protease Inhibitors; D013449:Sulfonamides; D013451:Sulfonic Acids; C075633:pepN protein, Bacteria; C002956:alanylalanine; D000626:Aminopeptidases