4mx1
Structure of ricin A chain bound with 2-amino-4-oxo-N-(2-(3-phenylureido)ethyl)-3,4-dihydropteridine-7-carboxamideStructure of ricin A chain bound with 2-amino-4-oxo-N-(2-(3-phenylureido)ethyl)-3,4-dihydropteridine-7-carboxamide
Structural highlights
Publication Abstract from PubMedSeveral 7-aminoamido-pterins were synthesized to evaluate the electronic and biochemical subtleties observed in the 'linker space' when N-{N-(pterin-7-yl)carbonylglycyl}-l-phenylalanine 1 was bound to the active site of RTA. The gylcine-phenylalanine dipeptide analogs included both amides and thioamides. Decarboxy gly-phe analog 2 showed a 6.4-fold decrease in potency (IC50 = 128 muM), yet the analogous thioamide 7 recovered the lost activity and performed similarly to the parent inhibitor (IC50 = 29 muM). Thiourea 12 exhibited an IC50 nearly six times lower than the oxo analog 13. All inhibitors showed the pterin head-group firmly bound in their X-ray structures yet the pendants were not fully resolved suggesting that all pendants are not firmly bound in the RTA linker space. Calculated log P values do not correlate to the increase in bioactivity suggesting other factors dominate. Sulfur incorporation generally improves Ricin inhibition in pterin-appended glycine-phenylalanine dipeptide mimics.,Wiget PA, Manzano LA, Pruet JM, Gao G, Saito R, Monzingo AF, Jasheway KR, Robertus JD, Anslyn EV Bioorg Med Chem Lett. 2013 Dec 15;23(24):6799-804. PMID:24432385[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences |
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