Application of crystallographic and modeling methods in the design of purine nucleoside phosphorylase inhibitors.
AUTOR(ES)
Ealick, S E
RESUMO
Competitive inhibitors of the salvage pathway enzyme purine-nucleoside phosphorylase (purine-nucleoside:orthophosphate ribosyltransferase, EC 2.4.2.1) have been designed by using the three-dimensional structure of the enzyme as determined by x-ray crystallography. The process was an iterative one that utilized interactive computer graphics, Monte Carlo-based conformational searching, energy minimization, and x-ray crystallography. The proposed compounds were synthesized and tested by an in vitro assay. Among the compounds designed and synthesized are the most potent competitive inhibitors of purine nucleoside phosphorylase thus far reported.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=53171Documentos Relacionados
- Application of crystallographic and modeling methods in the design of purine nucleoside phosphorylase inhibitors
- Rational design of inhibitors of Schistosoma mansoni purine nucleoside phosphorylase
- Sequence and functional characterization of the human purine nucleoside phosphorylase promoter.
- Design of vectors for efficient expression of human purine nucleoside phosphorylase in skin fibroblasts from enzyme-deficient humans.
- Purification and characterization of purine nucleoside phosphorylase from Proteus vulgaris.