Discovery of Highly Potent and Selective Inhibitors of Neuronal Nitric Oxide Synthase by Fragment Hopping

Abstract

Selective inhibition of neuronal nitric oxide synthase (nNOS) has been shown to prevent brain injury and is important for the treatment of various neurodegenerative disorders. This study shows that not only greater inhibitory potency and isozyme selectivity but more druglike properties can be achieved by fragment hopping.

Keywords

• amide bond peptidomimetics
• favorable binding-sites
• ligand probe groups
• 2 hydrogen-bonds
• de-novo design
• escherichia-coli
• active-site
• dipeptide amides
• drug discovery
• lead discovery