title: Synthesis and biological evaluation of phosphino dipeptide isostere inhibitor of human beta-secretase (BACE1).
abstract: Phosphino dipeptide (PDP) isosteres are known to be useful analogues of the transition state of metalloprotease substrates. Here we describe the use of this unit for the design of aspartic protease inhibitors. A PDP analogue of OM00-3, a potent BACE1 inhibitor, was synthesized and exhibited high biological activity (IC50 approximately 12 nM).
authors: Department Chemie, Lehrstuhl II für Organische Chemie, Technische Universität München, Lichtenbergstr. 4, 85747 Garching, Germany.
authors: Florian
authors: F
authors: Manzenrieder
authors: Andreas O
authors: AO
authors: Frank
authors: Timo
authors: T
authors: Huber
authors: Cornelia
authors: C
authors: Dorner-Ciossek
authors: Horst
authors: H
authors: Kessler
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors*; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors*; D002851:Chromatography, High Pressure Liquid; D004151:Dipeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry
chemical_list: D004151:Dipeptides; D004791:Enzyme Inhibitors; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human