RESUMEN

Low molecular weight peptidomimetic compounds based on O-malonyl tyrosine and O-carboxymethyl salicylic acid are potent inhibitors of PTP1B. Modifications of the N-terminal Boc-Phe moiety were undertaken in an effort to improve physical chemical properties and to achieve cellular activity. Although Phe ultimately proved to be the optimal N-terminal amino acid, several viable replacements for the Boc group were identified, two of which afforded analogues that were effective at enhancing the insulin-stimulated uptake of 2-deoxyglucose by L6 myocytes.

Asunto(s)

Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Proteínas Tirosina Fosfatasas/antagonistas & inhibidores , Salicilatos/química , Salicilatos/farmacología , Tirosina/análogos & derivados , Tirosina/química , Tirosina/farmacología , Animales , Células Cultivadas , Desoxiglucosa/farmacocinética , Humanos , Insulina/farmacología , Imitación Molecular , Músculo Esquelético/citología , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/metabolismo , Fenilalanina/química , Fenilalanina/farmacología , Proteína Tirosina Fosfatasa no Receptora Tipo 1 , Ratas , Dominios Homologos src