- Towards the development of activity-based probes for detection of lysine-specific demethylase-1 activity
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The implications of lysine-specific demethylase-1 (LSD1) in tumorigenesis have urged scientists to develop diagnostic tools in order to explore the function of this enzyme. In this work, we present our efforts on the development of tranylcypromine (TCP)-based functionalized probes for activity-based protein profiling (ABPP) of LSD1 activity. Biotinylated forms of selected compounds enabled dose-dependent enzyme labeling of recombinant LSD1. However, treatment with LSD1 inhibitors did not clearly reduce the LSD1 labeling efficiency thus indicating that labeling using these probes is not activity dependent. This calls for alternative strategies to develop probes for ABPP of the enzyme LSD1.
- Ourailidou, Maria E.,Lenoci, Alessia,Zwergel, Clemens,Rotili, Dante,Mai, Antonello,Dekker, Frank J.
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p. 847 - 856
(2017/02/05)
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- 5-[5-[2-(3,5-BIS(TRIFLUOROMETHYL)PHENYL)-2-METHYLPROPANOYLMETHYLAMINO]-4-(4-FLUORO-2-METHYLPHENYL)]-2-PYRIDINYL-2-ALKYL-PROLINAMIDE AS NK1 RECEPTOR ANTAGONISTS
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The invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof, wherein R is C1-4 alkyl useful in the treatment of diseases and conditions for which antagonism of NK1 receptor is beneficial.
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Page/Page column 43-44
(2009/12/23)
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- NOVEL B1 BRADYKININ RECEPTOR ANTAGONISTS
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The invention encompasses novel compounds of a formula I and pharmaceutically acceptable derivatives thereof, pharmaceutical compositions and methods for treatment of diseases mediated by B1 bradykinin receptor.
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Page/Page column 49-50
(2010/11/08)
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- Pd-catalyzed cyclization reactions of acetylene-containing α-amino acids
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Acetylene-containing amino acids, obtained in enantiopure form via an enzymatic resolution process, serve as versatile intermediates in the synthesis of various highly functionalized heterocycles. The key transformations, intramolecular OC- and NC-bond formation, proceed via Pd- catalysis.
- Wolf, Larissa B.,Tjen, Kim C. M. F.,Rutjes, Floris P. J. T.,Hiemstra, Henk,Schoemaker, Hans E.
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p. 5081 - 5084
(2007/10/03)
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- ENANTIOSELECTIVE SYNTHESIS OF NON-PROTEINOGENIC AMINO ACIDS VIA METALLATED BIS-LACTIM ETHERS OF 2,5-DIKETOPIPERAZINES
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Bis-lactim ethers 1 of 2,5-diketopiperazines contain a chiral inducing center, an acidic CH-bond and two sites susceptible to hydrolysis.They react with BuLi to give Li compounds of type 4, 15, 29 or 32, which possess a prochiral C atom.They readily add electrophiles (such as alkylating agents or carbonyl compounds) with unusually high diastereoface differentiation.In many cases the d.e-value (d.e. = diastereomeric excess = asymmetric induction) of the adduct exceeds 95percent.On hydrolysis the adducts are cleaved liberating the chiral auxiliary (used to build up the bis-lactim ether 1) and the target molecules, the optically active amino acid methyl esters of type 8, 19, 25 or 36.The two amino acid esters are separable either by fractional distillation or (eventually after further hydrolysis to amino acids) by chromatography.Transition state models are discussed that could explain the exceptionally high asymmetric induction and the predictability of the induced configuration.
- Schoellkopf, Ulrich
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p. 2085 - 2092
(2007/10/02)
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