1609090-72-3Relevant academic research and scientific papers
8-Triazolylpurines: Towards fluorescent inhibitors of the MDM2/p53 interaction
Pettersson, Mariell,Bliman, David,Jacobsson, Jimmy,Nilsson, Jesper R.,Min, Jaeki,Iconaru, Luigi,Guy, R. Kiplin,Kriwacki, Richard W.,Andréasson, Joakim,Gr?tli, Morten
, (2015/05/20)
Small molecule nonpeptidic mimics of α-helices are widely recognised as protein-protein interaction (PPIs) inhibitors. Protein-protein interactions mediate virtually all important regulatory pathways in a cell, and the ability to control and modulate PPIs is therefore of great significance to basic biology, where controlled disruption of protein networks is key to understanding network connectivity and function. We have designed and synthesised two series of 2,6,9-substituted 8-triazolylpurines as α-helix mimetics. The first series was designed based on low energy conformations but did not display any biological activity in a biochemical fluorescence polarisation assay targeting MDM2/p53. Although solution NMR conformation studies demonstrated that such molecules could mimic the topography of an α-helix, docking studies indicated that the same compounds were not optimal as inhibitors for the MDM2/p53 interaction. A new series of 8-triazolylpurines was designed based on a combination of docking studies and analysis of recently published inhibitors. The best compound displayed low micromolar inhibitory activity towards MDM2/p53 in a biochemical fluorescence polarisation assay. In order to evaluate the applicability of these compounds as biologically active and intrinsically fluorescent probes, their absorption/emission properties were measured. The compounds display fluorescent properties with quantum yields up to 50%.
8-Bromination of 2,6,9-trisubstituted purines with pyridinium tribromide
Bliman, David,Pettersson, Mariell,Bood, Mattias,Gr?tli, Morten
supporting information, p. 2929 - 2931 (2014/05/06)
2,6,9-Trisubstituted purines are brominated in high yields using pyridinium tribromide as the brominating reagent. This procedure works excellently for electron-rich purines having electron-donating substituents at the 2- and 6-positions. The use of pyridinium tribromide, a crystalline alternative to elemental bromine, improves the bromination procedure for this type of substrate as the reagent is easy to handle and the work-up and purification procedures are simplified.
