[GRAPHICS]
One drawback frequently associated with olefin metathesis-mediated peptide
macrocyclization, the loss of side chain functionality at sites of ring clo
sure, may be circumvented by incorporation of side chain functionality with
in the ring-closing olefin segments, This approach is demonstrated in the p
reparation of a macrocyclic Grb2 SH2 domain antagonist designed as a confor
mationally constrained beta -bend mimic.