title: Selectively guanidinylated derivatives of neamine. Syntheses and inhibition of anthrax lethal factor protease.
abstract: 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.
authors.affiliation: Department of Chemistry, Hawaii Biotech, Inc., 99-193 Aiea Heights Dr., Suite 200, Aiea, 96701, USA. gjiao@hibiotech.com
authors.forename: Guan-Sheng
authors.initials: GS
authors.lastname: Jiao
authors.forename: Ondrej
authors.initials: O
authors.lastname: Simo
authors.forename: Melissa
authors.initials: M
authors.lastname: Nagata
authors.forename: Sean
authors.initials: S
authors.lastname: O'Malley
authors.forename: Thomas
authors.initials: T
authors.lastname: Hemscheidt
authors.forename: Lynne
authors.initials: L
authors.lastname: Cregar
authors.forename: Sherri Z
authors.initials: SZ
authors.lastname: Millis
authors.forename: Mark E
authors.initials: ME
authors.lastname: Goldman
authors.forename: Cho
authors.initials: C
authors.lastname: Tang
mesh_terms: 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
chemical_list: D000617:Aminoglycosides; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D004791:Enzyme Inhibitors; C030325:anthrax toxin; D005601:Framycetin; C488396:neamine; D008666:Metalloendopeptidases; D019791:Guanidine