RESUMEN
Attempts to identify the prenyl-proteome of cells or changes in prenylation following drug treatment have used 'clickable' alkyne-modified analogs of the lipid substrates farnesyl- and geranylgeranyl-diphosphate (FPP and GGPP). We characterized the reactivity of four alkyne-containing analogs of FPP with purified protein farnesyltransferase and a small library of dansylated peptides using an in vitro continuous spectrofluorimetric assay. These analogs alter prenylation specificity and reactivity suggesting that in vivo results obtained using these FPP analogs should be interpreted cautiously.
Asunto(s)
Transferasas Alquil y Aril/metabolismo , Fosfatos de Poliisoprenilo/metabolismo , Sesquiterpenos/metabolismo , Alquinos/química , Química Clic , Cinética , Péptidos/química , Péptidos/metabolismo , Fosfatos de Poliisoprenilo/química , Prenilación de Proteína , Sesquiterpenos/química , Especificidad por SustratoRESUMEN
A [3,3]-rearrangement that is used for facile construction of chiral allenamides is described. A propargylic alcohol, a chlorophosphite, and Cbz-azide are combined to provide a propargylic phosphorimidate that, in the presence of catalytic palladium(II), rearranges to an allenamide. By varying the substitution pattern on the propargylic alcohol, mono-, di-, and trisubstituted allenamides can be accessed in good yields. Additionally, the use of an enantiomerically enriched propargylic alcohol enables the preparation of stereochemically defined allenamides.
