title: 7-Substituted pterins provide a new direction for ricin A chain inhibitors.
abstract: Ricin is a potent toxin found in castor seeds. The A chain, RTA, enzymaticlly depurinates a specific adenosine in ribosomal RNA, inhibiting protein synthesis. Ricin is a known chemical weapons threat having no effective antidote. This makes the discovery of new inhibitors of great importance. We have previously used 6-substituted pterins, such as pteroic acid, as an inhibitor platform with moderate success. We now report the success of 7-carboxy pterin (7CP) as an RTA inhibitor; its binding has been monitored using both kinetic and temperature shift assays and by X-ray crystallography. We also discuss the synthesis of various derivatives of 7CP, and their binding affinity and inhibitory effects, as part of a program to make effective RTA inhibitors.
authors.affiliation: Department of Chemistry and Biochemistry, University of Texas at Austin, 1 University Station A1590, Austin, TX 78712, USA.
authors.forename: Jeff M
authors.initials: JM
authors.lastname: Pruet
authors.forename: Karl R
authors.initials: KR
authors.lastname: Jasheway
authors.forename: Lawrence A
authors.initials: LA
authors.lastname: Manzano
authors.forename: Yan
authors.initials: Y
authors.lastname: Bai
authors.forename: Eric V
authors.initials: EV
authors.lastname: Anslyn
authors.forename: Jon D
authors.initials: JD
authors.lastname: Robertus
mesh_terms: D018360:Crystallography, X-Ray; D005470:Fluorometry; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D011622:Pterins / Q000737:chemistry / Q000494:pharmacology*; D012276:Ricin / Q000037:antagonists & inhibitors*; D021241:Spectrometry, Mass, Electrospray Ionization; D013696:Temperature
chemical_list: D011622:Pterins; D012276:Ricin