RESUMO
A series of neoglycoconjugates derived from deoxynojirimycin has been prepared by click connection with functionalised adamantanes. They have been assayed as glycosidase inhibitors, as inhibitors of the glycoenzymes relevant to the treatment of Gaucher disease, as well as correctors of the defective ion-transport protein involved in cystic fibrosis. We have demonstrated that it is possible to selectively either strongly inhibit ER-α-glucosidases and ceramide glucosyltransferase or restore the activity of CFTR in CF-KM4 cells by varying the length of the alkyl chain linking DNJ and adamantane.
Assuntos
1-Desoxinojirimicina/química , Antivirais/química , Inibidores Enzimáticos/química , Glicoconjugados/química , Animais , Linhagem Celular , Cromatografia Líquida de Alta Pressão , Química Click , Ativação Enzimática/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Células HL-60 , Humanos , Concentração Inibidora 50 , Estrutura Molecular , Ratos , Bibliotecas de Moléculas Pequenas/químicaRESUMO
Despite the importance of the isocyanate group in chemistry, very few examples of isocyanate-modified silicas have been reported, and all of the strategies described so far led to partial or total hydrolysis or condensation of the isocyanate group. By synthesizing trichlorosilane isocyanate as the coupling reagent, we show that oxidized silicon wafers are successfully modified with the isocyanate group. Our method is achieved in mild conditions, at low temperature, without side-reactions and allows the formation of a self-assembled monolayer (SAM) of isocyanates. The isocyanate group then offers a flexible way to further functionalize silica substrates with different nucleophiles, due to its high and specific reactivity.
