title: Exploration of the one-bead one-compound methodology for the design of prolyl oligopeptidase substrates.
abstract: Here we describe the design, synthesis and evaluation of the first solid-phase substrates for prolyl oligopeptidase (POP), a cytosolic serine peptidase associated with schizophrenia, bipolar affective disorder and related neuropsychiatric disorders. This study seeks to contribute to the future design of a one-bead one-compound (OBOC) peptide library of POP substrates, based on an intramolecular energy transfer substrate. Unexpectedly, the enzymatic evaluation of the substrates attached on solid-phase by means of the HMBA linker were cleaved through the ester bond, thereby suggesting an unknown esterase activity of POP, in addition to its known peptidase activity. By performing multiple activity assays, we have confirmed the esterase activity of this enzyme and its capacity to process the substrates on solid-phase. Finally, we tested a new linker, compatible with both the solid-phase peptide-synthesis used and the enzymatic assay, for application in the future design of an OBOC library.
authors: Institut de Recerca Biomèdica (IRB Barcelona), Parc Científic de Barcelona, Barcelona, Spain.
authors: Gemma
authors: G
authors: Comellas
authors: Zusanna
authors: Z
authors: Kaczmarska
authors: Teresa
authors: T
authors: Tarragó
authors: Meritxell
authors: M
authors: Teixidó
authors: Ernest
authors: E
authors: Giralt
mesh_terms: D002851:Chromatography, High Pressure Liquid; D000085822:Prolyl Oligopeptidases; D012697:Serine Endopeptidases / Q000378:metabolism*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013056:Spectrophotometry, Ultraviolet; D013379:Substrate Specificity
chemical_list: D012697:Serine Endopeptidases; D000085822:Prolyl Oligopeptidases