title: 3-(aminomethyl)piperazine-2,5-dione as a novel NMDA glycine site inhibitor from the chemical universe database GDB.
abstract: Docking of randomly selected compounds from the chemical universe database GDB-11, which contains all organic molecules up to 11 atoms of C, N, O, F possible under consideration of simple chemical stability and synthetic feasibility rules, into the NMDA receptor glycine site (1pb7.pdb) lead to the identification of 3-(aminomethyl)piperazine-2,5-dione 3 and its close analog 5-(aminomethyl)piperazine-2,3-dione 4 as possible new ligands for this drug target, which is implicated in synaptic plasticity, neuronal development, learning and memory. Synthesis of these compounds in 4 and 6 steps, respectively, and testing by radioligand displacement assays and electrophysiological measurements in Xenopus oocytes show that while 4 is inactive, 3 is indeed an inhibitor of glycine, with an estimated K(D) of 50 microM.
authors.affiliation: Department of Chemistry and Biochemistry, University of Berne, Berne, Switzerland.
authors.forename: Kong Thong
authors.initials: KT
authors.lastname: Nguyen
authors.forename: Erika
authors.initials: E
authors.lastname: Luethi
authors.forename: Salahuddin
authors.initials: S
authors.lastname: Syed
authors.forename: Stephan
authors.initials: S
authors.lastname: Urwyler
authors.forename: Sonia
authors.initials: S
authors.lastname: Bertrand
authors.forename: Daniel
authors.initials: D
authors.lastname: Bertrand
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Reymond
mesh_terms: D000818:Animals; D001665:Binding Sites; D003198:Computer Simulation; D016208:Databases, Factual; D054659:Diketopiperazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D005998:Glycine / Q000737:chemistry*; D009865:Oocytes / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012984:Software; D013816:Thermodynamics; D014982:Xenopus laevis
chemical_list: C544464:3-(aminomethyl)piperazine-2,5-dione; C544466:5-(aminomethyl)piperazine-2,3-dione; D054659:Diketopiperazines; D016194:Receptors, N-Methyl-D-Aspartate; D005998:Glycine