RESUMO
Four different conjugated polymer nanoparticles (CPNs) were used to differentiate structurally similar glycosaminoglycans (GAGs) in a urine simulant. Unique emission response patterns of CPNs were analyzed by linear discriminant analysis (LDA), confirming that structurally diverse CPNs are sensitive and effective at differentiating GAGs in a complex biological medium.
Assuntos
Materiais Biomiméticos/química , Glicosaminoglicanos/química , Nanopartículas/química , Polímeros/química , Urina , Absorção Fisico-QuímicaRESUMO
The ability to identify the site of a protein that can bind with high affinity to small, drug-like compounds has been an important goal in drug design. Sirtuin 2 (SIRT2), histone deacetylase protein family, plays a central role in the regulation of various pathways. Hence, identification of drug for SIRT2 has attracted great interest in the drug discovery community. To elucidate the molecular basis of the small molecules interactions to inhibit the SIRT2 function we employed the molecular docking, molecular dynamics simulations, and the molecular mechanism Poisson-Boltzmann/surface area (MM-PBSA) calculations. Five well know inhibitors such as suramin, mol-6, sirtinol, 67, and nf675 were selected to establish the nature of the binding mode of the inhibitors in the SIRT2 active site. The molecular docking and dynamics simulations results revealed that the hydrogen bonds between Arg97 and Gln167 are crucial to inhibit the function of SIRT2. In addition, the MM-PBSA calculations revealed that binding of inhibitors to SIRT2 is mainly driven by van der Waals/non-polar interactions. Although the five inhibitors are very different in structure, shape, and electrostatic potential, they are able to fit in the same binding pocket. These findings from this study provide insights to elucidate the binding pattern of SIRT2 inhibitors and help in the rational structure-based design of novel SIRT2 inhibitors with improved potency and better resistance profile.
Assuntos
Inibidores de Histona Desacetilases/química , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Sirtuína 2/química , Sítios de Ligação , Domínio Catalítico , Descoberta de Drogas , Humanos , Ligação de Hidrogênio , Conformação Proteica , Sirtuína 2/antagonistas & inibidores , Sirtuína 2/ultraestrutura , Relação Estrutura-Atividade , TermodinâmicaRESUMO
Benzimidazoles were synthesized by the copper-catalyzed, one-pot, three-component reaction of 2-haloanilines, aldehydes, and NaN(3). The reaction was optimized when 2-iodo- or 2-bromoanilines (1.0 equiv), aldehydes (1.2 equiv), NaN(3) (2.0 equiv), 5 mol% of CuCl, and 5 mol % of TMEDA were reacted in DMSO at 120 °C for 12 h. Good yields resulted, and the reaction showed tolerance toward functional groups such as ester, nitro, and chloro. Aliphatic and heteroaromatic aldehydes also afforded the desired products in moderate to good yields.
Assuntos
Benzimidazóis/síntese química , Cobre/química , Compostos Organometálicos/química , Benzimidazóis/química , Catálise , Estrutura Molecular , EstereoisomerismoRESUMO
2H-Indazoles are synthesized using copper-catalyzed, one-pot, three-component reactions of 2-bromobenzaldehydes, primary amines, and sodium azide. A copper catalyst plays the key role in the formation of C-N and N-N bonds. This method has a broad substrate scope with a high tolerance for a variety of functional groups.