Assuntos
Bactérias/efeitos dos fármacos , Bactérias/enzimologia , Desenho de Fármacos , Glicosiltransferases/antagonistas & inibidores , Glicosiltransferases/metabolismo , Peptídeos/farmacologia , Uridina Difosfato Ácido N-Acetilmurâmico/análogos & derivados , Sítios de Ligação , Parede Celular/química , Parede Celular/efeitos dos fármacos , Parede Celular/metabolismo , Glicosiltransferases/química , Relação Estrutura-Atividade , Uridina Difosfato Ácido N-Acetilmurâmico/químicaRESUMO
The preparation of a novel fluorescent lipid II-based substrate for transglycosylases (TGases) is described. This substrate has characteristic structural features including a shorter lipid chain, a fluorophore tag at the end of the lipid chain rather than on the peptide chain, and no labeling with a radioactive atom. This fluorescent substrate is readily utilized in TGase activity assays to characterize TGases and also to evaluate the activities of TGase inhibitors.
Assuntos
Fluorescência , Glicosiltransferases/metabolismo , Fosfatos de Poli-Isoprenil/síntese química , Fosfatos de Poli-Isoprenil/metabolismo , Uridina Difosfato Ácido N-Acetilmurâmico/análogos & derivados , Bambermicinas/farmacologia , Inibidores Enzimáticos/farmacologia , Glicosiltransferases/antagonistas & inibidores , Estrutura Molecular , Fosfatos de Poli-Isoprenil/química , Relação Estrutura-Atividade , Especificidade por Substrato , Uridina Difosfato Ácido N-Acetilmurâmico/química , Uridina Difosfato Ácido N-Acetilmurâmico/metabolismoRESUMO
Solid-phase organic synthesis of polyprenols with a traceless sulfone linker is described. The polymer-bound benezenesulfinate is first linked with the "tail" building blocks of isoprenyl chlorides via S-alkylation. With use of dimsyl anion as an appropriate base, the polymer-bound alpha-sulfonyl carbanion is generated and coupled with other "body" building blocks in an efficient manner. After repeated processes and a global palladium-catalyzed desulfonation with LiEt 3BH as the reducing agent, the desired polyprenols with various chain lengths and geometrical configurations are obtained in 32-59% overall yields. The solid-phase synthesis offers the advantage in facile isolation of polyprenols without tedious operation or time-consuming purification.