title: Peptide-conjugated pterins as inhibitors of ricin toxin A.
abstract: Several 7-peptide-substituted pterins were synthesized and tested as competitive active-site inhibitors of ricin toxin A (RTA). Focus began on dipeptide conjugates, and these results further guided the construction of several tripeptide conjugates. The binding of these compounds to RTA was studied via a luminescence-based kinetic assay, as well as through X-ray crystallography. Despite the relatively polar, solvent exposed active site, several hydrophobic interactions, most commonly π-interactions not predicted by modeling programs, were identified in all of the best-performing inhibitors. Nearly all of these compounds provide IC₅₀ values in the low micromolar range.
authors.affiliation: Department of Chemistry, Toho University, 2-2-1 Miyama, Funabashi 274-8510, Japan. anslyn@austin.utexas.edu
authors.forename: Ryota
authors.initials: R
authors.lastname: Saito
authors.forename: Jeff M
authors.initials: JM
authors.lastname: Pruet
authors.forename: Lawrence A
authors.initials: LA
authors.lastname: Manzano
authors.forename: Karl
authors.initials: K
authors.lastname: Jasheway
authors.forename: Arthur F
authors.initials: AF
authors.lastname: Monzingo
authors.forename: Paul A
authors.initials: PA
authors.lastname: Wiget
authors.forename: Ishan
authors.initials: I
authors.lastname: Kamat
authors.forename: Eric V
authors.initials: EV
authors.lastname: Anslyn
authors.forename: Jon D
authors.initials: JD
authors.lastname: Robertus
mesh_terms: D001667:Binding, Competitive; D020134:Catalytic Domain; D002619:Chemical Warfare Agents / Q000737:chemistry; D018360:Crystallography, X-Ray; D057927:Hydrophobic and Hydrophilic Interactions; D007700:Kinetics; D008163:Luminescent Measurements; D008958:Models, Molecular; D015394:Molecular Structure; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011485:Protein Binding; D011622:Pterins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D012276:Ricin / Q000037:antagonists & inhibitors* / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D002619:Chemical Warfare Agents; D009842:Oligopeptides; D011622:Pterins; D012276:Ricin