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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 ?-interactions not predicted by modeling programs, were identified in all of the best-performing inhibitors. Nearly all of these compounds provide IC?? values in the low micromolar range.

SUBMITTER: Saito R

PROVIDER: S-EPMC3552522 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature

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Peptide-conjugated pterins as inhibitors of ricin toxin A.

Saito Ryota R Pruet Jeff M JM Manzano Lawrence A LA Jasheway Karl K Monzingo Arthur F AF Wiget Paul A PA Kamat Ishan I Anslyn Eric V EV Robertus Jon D JD

Journal of medicinal chemistry 20121219 1

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-interactio ...[more]

PMID: 23214944

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