Format

Send to

Choose Destination
Bioorg Med Chem Lett. 2008 Feb 1;18(3):1031-6. doi: 10.1016/j.bmcl.2007.12.028. Epub 2008 Jan 3.

Potent memapsin 2 (beta-secretase) inhibitors: design, synthesis, protein-ligand X-ray structure, and in vivo evaluation.

Author information

1
Department of Chemistry, Purdue University, West Lafayette, IN 47907, USA. akghosh@purdue.edu

Abstract

Structure-based design, synthesis, and biological evaluation of a series of peptidomimetic beta-secretase inhibitors incorporating hydroxyethylamine isosteres are described. We have identified inhibitor 24 which has shown exceedingly potent activity in memapsin 2 enzyme inhibitory (K(i) 1.8 nM) and cellular (IC(50)=1 nM in Chinese hamster ovary cells) assays. Inhibitor 24 has also shown very impressive in vivo properties (up to 65% reduction of plasma A beta) in transgenic mice. The X-ray structure of protein-ligand complex of memapsin 2 revealed critical interactions in the memapsin 2 active site.

PMID:
18180160
PMCID:
PMC2577816
DOI:
10.1016/j.bmcl.2007.12.028
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center