75647-01-7Relevant articles and documents
Substrate specificity of an actively assembling amyloid catalyst
Heier, Jason L.,Mikolajczak, Dorian J.,B?ttcher, Christoph,Koksch, Beate
, (2017/02/05)
In the presence of Zn2+, the catalytic, amyloid-forming peptide Ac-IHIHIQI-NH2, was found to exhibit enhanced selectivity for hydrophobic p-nitrophenyl ester substrates while in the process of self-assembly. As opposed to the substrate p-nitrophenyl acetate, which was more effectively hydrolyzed with Ac-IHIHIQI-NH2 in its fully fibrillar state, the hydrophobic substrate Z-L-Phe-ONp was converted with a second-order rate constant more than 11-times greater when the catalyst was actively assembling. Under such conditions, Z-L-Phe-ONp hydrolysis proceeded at a greater velocity than the more hydrophilic and otherwise more labile ester Boc-L-Asn-ONp. When assembling, the catalyst also showed increased selectivity for the L-enantiomer of Z-Phe-ONp. These findings suggest the occurrence of increased interactions of hydrophobic moieties of the substrate with exposed hydrophobic surfaces of the assembling peptides and present valuable features for future de novo design consideration.
Amino acid conjugates of lithocholic acid as antagonists of the EphA2 receptor
Incerti, Matteo,Tognolini, Massimiliano,Russo, Simonetta,Pala, Daniele,Giorgio, Carmine,Hassan-Mohamed, Iftiin,Noberini, Roberta,Pasquale, Elena B.,Vicini, Paola,Piersanti, Silvia,Rivara, Silvia,Barocelli, Elisabetta,Mor, Marco,Lodola, Alessio
supporting information, p. 2936 - 2947 (2013/05/22)
The Eph receptor-ephrin system is an emerging target for the development of novel antiangiogenetic agents. We recently identified lithocholic acid (LCA) as a small molecule able to block EphA2-dependent signals in cancer cells, suggesting that its (5β)-cholan-24-oic acid scaffold can be used as a template to design a new generation of improved EphA2 antagonists. Here, we report the design and synthesis of an extended set of LCA derivatives obtained by conjugation of its carboxyl group with different α-amino acids. Structure-activity relationships indicate that the presence of a lipophilic amino acid side chain is fundamental to achieve good potencies. The l-Trp derivative (20, PCM126) was the most potent antagonist of the series disrupting EphA2-ephrinA1 interaction and blocking EphA2 phosphorylation in prostate cancer cells at low μM concentrations, thus being significantly more potent than LCA. Compound 20 is among the most potent small-molecule antagonists of the EphA2 receptor.
KINASE INHIBITOR COMPOUNDS
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Page/Page column 86, (2008/06/13)
The invention relates to compounds, compositions comprising the compounds, and methods of using the compounds and compound compositions. The compounds, compositions, and methods described herein can be used for the therapeutic modulation of kinase-mediated processes, and treatment of disease and disease symptoms, particularly those mediated by certain kinase enzymes.
