Protection against anthrax toxemia by hexa-D-arginine in vitro and in vivo.
The anthrax toxin protective antigen precursor is activated by proteolytic cleavage by furin or a furin-like protease. We present here data demonstrating that the small stable furin inhibitor hexa-D-arginine amide delays anthrax toxin-induced toxemia both in cells and in live animals, suggesting that furin inhibition may represent a reasonable avenue for therapeutic intervention in anthrax.
Sarac
Miroslav S
MS
Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112, USA.
Peinado
Juan R
JR
Leppla
Stephen H
SH
Lindberg
Iris
I
D000818:Animals; D000881:Anthrax / Q000517:prevention & control*; D000942:Antigens, Bacterial; D001427:Bacterial Toxins / Q000633:toxicity*; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000008:administration & dosage*; D045683:Furin / Q000037:antagonists & inhibitors*; D016676:Macrophages, Alveolar / Q000473:pathology; D008297:Male; D010455:Peptides / Q000008:administration & dosage*; D051381:Rats; D011916:Rats, Inbred F344; D014115:Toxemia / Q000517:prevention & control*
D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D004791:Enzyme Inhibitors; D010455:Peptides; C030325:anthrax toxin; C015462:polyarginine; D045683:Furin