Selectively guanidinylated derivatives of neamine. Syntheses and inhibition of anthrax lethal factor protease.
A series of mono-, di-, and tri-guanidinylated derivatives of neamine were prepared via selective guanidinylation of neamine. These molecules represent a novel scaffold as inhibitors of anthrax lethal factor zinc metalloprotease. Methods for the synthesis of these compounds are described, and structure-activity relationships among the series are analyzed. In addition, initial findings regarding the mechanism of LF inhibition for these molecules are presented.
Jiao
Guan-Sheng
GS
Department of Chemistry, Hawaii Biotech, Inc., 99-193 Aiea Heights Dr., Suite 200, Aiea, 96701, USA. gjiao@hibiotech.com
Simo
Ondrej
O
Nagata
Melissa
M
O'Malley
Sean
S
Hemscheidt
Thomas
T
Cregar
Lynne
L
Millis
Sherri Z
SZ
Goldman
Mark E
ME
Tang
Cho
C
D000617:Aminoglycosides / Q000138:chemical synthesis* / Q000494:pharmacology*; D000942:Antigens, Bacterial; D001408:Bacillus anthracis / Q000201:enzymology; D001427:Bacterial Toxins / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D005601:Framycetin / Q000138:chemical synthesis* / Q000494:pharmacology*; D019791:Guanidine / Q000737:chemistry; D007700:Kinetics; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors; D013329:Structure-Activity Relationship
D000617:Aminoglycosides; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D004791:Enzyme Inhibitors; C030325:anthrax toxin; D005601:Framycetin; C488396:neamine; D008666:Metalloendopeptidases; D019791:Guanidine