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.
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.
