Publication Abstract from PubMed
The hydroxyethylene octapeptide inhibitor OM99-2 served as starting point to create the tripeptide inhibitor 1 and its analogues 2a and b. An X-ray co-crystal structure of 1 with BACE-1 allowed the design and syntheses of a series of macrocyclic analogues 3a-h covalently linking the P1 and P3 side-chains. These inhibitors show improved enzymatic potency over their open-chain analogue. Inhibitor 3h also shows activity in a cellular system.
Structure-based design and synthesis of macrocyclic peptidomimetic beta-secretase (BACE-1) inhibitors.,Machauer R, Veenstra S, Rondeau JM, Tintelnot-Blomley M, Betschart C, Neumann U, Paganetti P Bioorg Med Chem Lett. 2009 Mar 1;19(5):1361-5. Epub 2009 Jan 19. PMID:19195886[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
