Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10593344 | Bioorganic & Medicinal Chemistry Letters | 2013 | 6 Pages |
Abstract
Several 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 μM), yet the analogous thioamide 7 recovered the lost activity and performed similarly to the parent inhibitor (IC50 = 29 μM). 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.
Related Topics
Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
Paul A. Wiget, Lawrence A. Manzano, Jeff M. Pruet, Grace Gao, Ryota Saito, Arthur F. Monzingo, Karl R. Jasheway, Jon D. Robertus, Eric V. Anslyn,