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Search results for: Benzyl

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#35972884   2022/08/16 To Up

Small Changes Make the Difference for SIRT2: Two Different Binding Modes for 3-Arylmercapto-Acylated Lysine Derivatives.

Sirtuins are protein deacylases regulating metabolism and stress responses and implicated in aging-related diseases. Modulators of the human sirtuins 1-7 are sought as chemical tools and potential therapeutics, for example, for treatment of cancer. We were able to show that 3-aryl-mercapto-succinylated- and 3-benzyl-mercapto-succinylated peptide derivatives yield selective Sirt5 inhibitors with low nM values. Here, we synthesized and characterized 3-aryl-mercapto-butyrylated peptide derivatives as effective and selective sirtuin 2 inhibitors with values in the low nanomolar range. According to kinetic measurements and microscale thermophoresis/surface plasmon resonance experiments, the respective inhibitors bind with the 3-aryl-mercapto moiety in the selectivity pocket of Sirtuin 2, inducing a rearrangement of the active site. In contrast, 3-aryl-mercapto-nonalyl or palmitoyl derivatives are characterized by a switch in the binding mode blocking both the hydrophobic channel by the fatty acyl chain and the nicotinamide pocket by the 3-aryl-mercapto moiety.
Diana Kalbas, Marat Meleshin, Sandra Liebscher, Matthes Zessin, Jelena Melesina, Cordelia Schiene-Fischer, Emre Fatih Bülbül, Frank Bordusa, Wolfgang Sippl, Mike Schutkowski

2715 related Products with: Small Changes Make the Difference for SIRT2: Two Different Binding Modes for 3-Arylmercapto-Acylated Lysine Derivatives.

20 ug0.2 mg1 g250 mg96 Tests100 mg 500 ml 100 mg96 Well25 g

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#35972316   2022/08/16 To Up

Synthesis of -stilbenes phosphine-catalyzed coupling reactions of benzylic halides.

An efficient and practical phosphine-catalyzed homo-coupling reaction of benzyl chlorides is described. The reactions proceed smoothly in the presence of CsF/B(OMe) and NaH as the base, respectively, to provide -stilbenes in good yields with a broad scope. Unsymmetrical stilbenes are also generated from the reactions of benzyl chlorides with phosphonium salts. Several P-based key intermediates have been detected by NMR and HRMS analyses, which shed light on the postulated catalytic cycle. In the presence of different bases, the transformations involve two different pathways, in which phenylcarbene and phosphonium alkoxide are considered as key intermediates, respectively. The two pathways are complementary in synthesis but different in mechanisms. The synthetic utility, including gram-scale reactions and straightforward access to π-conjugated molecules, has been demonstrated as well.
Sheng Zhang, Zhilong Xie, Zhanqiang Ye, Mingyang Zhang, Dongdeng Li, Masahiko Yamaguchi, Ming Bao

2148 related Products with: Synthesis of -stilbenes phosphine-catalyzed coupling reactions of benzylic halides.