Tailoring Small Molecules for an Allosteric Site on Procaspase-6 was written by Murray, Jeremy;Giannetti, Anthony M.;Steffek, Micah;Gibbons, Paul;Hearn, Brian R.;Cohen, Frederick;Tam, Christine;Pozniak, Christine;Bravo, Brandon;Lewcock, Joe;Jaishankar, Priyadarshini;Ly, Cuong Q.;Zhao, Xianrui;Tang, Yinyan;Chugha, Preeti;Arkin, Michelle R.;Flygare, John;Renslo, Adam R.. And the article was included in ChemMedChem in 2014.Formula: C9H7NO This article mentions the following:
Although they represent attractive therapeutic targets, caspases have so far proven recalcitrant to the development of drugs targeting the active site. Allosteric modulation of caspase activity is an alternate strategy that potentially avoids the need for anionic and electrophilic functionality present in most active-site inhibitors. Caspase-6 has been implicated in neurodegenerative disease, including Huntington’s and Alzheimer’s diseases. Herein we describe a fragment-based lead discovery effort focused on caspase-6 in its active and zymogen forms. Fragments were identified for procaspase-6 using surface plasmon resonance methods and subsequently shown by X-ray crystallog. to bind a putative allosteric site at the dimer interface. A fragment-merging strategy was employed to produce nanomolar-affinity ligands that contact residues in the L2 loop at the dimer interface, significantly stabilizing procaspase-6. Because rearrangement of the L2 loop is required for caspase-6 activation, our results suggest a strategy for the allosteric control of caspase activation with drug-like small mols. In the experiment, the researchers used many compounds, for example, 1-Hydroxyisoquinoline (cas: 491-30-5Formula: C9H7NO).
1-Hydroxyisoquinoline (cas: 491-30-5) belongs to isoquinoline derivatives. Quinoline and isoquinoline skeletons are among the most attractive frameworks with a wide range of biological and pharmacological activities. The Pomeranz鈥揊ritsch reaction provides a method for the preparation of isoquinoline. This reaction uses a benzaldehyde and aminoacetoaldehyde diethyl acetal, which in an acid medium react to form isoquinoline.Formula: C9H7NO
Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem