Synthesis of an external β-turn based on the GLDV motif of cell adhesion proteins

The (3S,6S,10S)-7/5 bicyclic lactam 4, designed as an external turn constraint, was synthesised by a new stereoselective route involving Eschenmoser condensation. Calculated preferred conformations compare well with the preferred solid state conformation, obtained by X-ray crystallography. The lactam 4 was not a turn mimic in its own right but could be used as an external constraint to prepare the cyclic peptide 29 containing the integrin recognition motif GLDV. High-resolution NMR measurements were consistent with this compound having a single backbone conformation.