title: Guanidinylated 2,5-dideoxystreptamine derivatives as anthrax lethal factor inhibitors.
abstract: Anthrax lethal factor is a Zn(2+)-dependent metalloprotease and the key virulence factor of tripartite anthrax toxin secreted by Bacillus anthracis, the causative agent of anthrax. A series of guanidinylated 2,5-dideoxystreptamine derivatives were designed and synthesized as inhibitors of lethal factor, some of which show strong inhibitory activity against lethal factor in an in vitro FRET assay. Preparation and structure-activity relationships of these compounds are presented.
authors.affiliation: Department of Chemistry, Hawaii Biotech Inc., 99-193 Aiea Heights Drive, Suite 200, Aiea, HI 96701, USA. gjiao@hibiotech.com
authors.forename: Guan-Sheng
authors.initials: GS
authors.lastname: Jiao
authors.forename: Lynne
authors.initials: L
authors.lastname: Cregar
authors.forename: Mark E
authors.initials: ME
authors.lastname: Goldman
authors.forename: Sherri Z
authors.initials: SZ
authors.lastname: Millis
authors.forename: Cho
authors.initials: C
authors.lastname: Tang
mesh_terms: D001408:Bacillus anthracis / Q000201:enzymology*; D001427:Bacterial Toxins / Q000037:antagonists & inhibitors*; D019791:Guanidine / Q000737:chemistry*; D006595:Hexosamines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors*; D008958:Models, Molecular; D015394:Molecular Structure; D011480:Protease Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D001427:Bacterial Toxins; D006595:Hexosamines; D011480:Protease Inhibitors; C002980:streptamine; D008666:Metalloendopeptidases; D019791:Guanidine