α-Dicarbonyls as “non-charged” arginine-directed affinity labels. Novel synthetic routes to α-dicarbonyl analogs of the PP60c-src SH2 domain-targeted phosphopeptide Ac-Tyr(OPO3H2)-Glu-Glu-Ile-Glu

The phosphopeptide 1 is a potent inhibitor of pp60c-src SH2 domain mediated phosphoprotein interactions (IC50 ≤ 0.5 μM), but lacks cell permeability. The syntheses of its less charged analogs 2 and 3 are described, in which the arginine-binding phosphate group has been substituted with uncharged α-dicarbonyl moieties. The chemistry described here may be of general use for the synthesis of other α-dicarbonyl compounds.