Synthesis and biological evaluation of reversible inhibitors of IdeS, a bacterial cysteine protease and virulence determinant.
Analogues of the irreversible protease inhibitors TPCK and TLCK have been synthesized and tested as inhibitors of the bacterial cysteine protease IdeS excreted by Streptococcuspyogenes. Eight compounds were identified as inhibitors of IdeS in an in vitro assay. The most potent compounds contained an aldehyde function, thus acting as efficient reversible inhibitors, nitrile and azide derivatives showed moderate activity.
Department of Chemistry, Medicinal Chemistry, University of Gothenburg, Göteborg, Sweden.
Kristina
K
Berggren
Björn
B
Johansson
Tomas
T
Fex
Jan
J
Kihlberg
Lars
L
Björck
Kristina
K
Luthman
D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D003546:Cysteine Endopeptidases / Q000737:chemistry / Q000378:metabolism*; D057056:Cysteine Proteases / Q000378:metabolism; D015853:Cysteine Proteinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D007700:Kinetics; D011485:Protein Binding; D013297:Streptococcus pyogenes / Q000201:enzymology / Q000472:pathogenicity; D013329:Structure-Activity Relationship; D014107:Tosyllysine Chloromethyl Ketone / Q000737:chemistry / Q000494:pharmacology; D014108:Tosylphenylalanyl Chloromethyl Ketone / Q000737:chemistry / Q000494:pharmacology; D014774:Virulence
D001426:Bacterial Proteins; D015853:Cysteine Proteinase Inhibitors; C442815:Mac-1-like protein, Streptococcus; D014107:Tosyllysine Chloromethyl Ketone; D014108:Tosylphenylalanyl Chloromethyl Ketone; D057056:Cysteine Proteases; D003546:Cysteine Endopeptidases