The design of polar β-turn dipeptide mimetics

The design and synthesis of conformationally constrained, non-peptide templates (3-substituted pyrrolidines) which allow the incorporation of two adjacent amino acid side-chains in an orientation similar to that found in the i+1 and i+1 positions of a β-turn are reported. The NK2 tachykinin receptor affinity of a Trp-Phe mimetic (7a) which mimics the β-turn in MEN10627 (8), a constrained cyclic hexapeptide, high affinity NK2 tachykinin receptor antagonist, was determined and shown to have no significant binding affinity (NK2, IC50> 10,000 nM).