THE DESIGN OF POLAR BETA-TURN DIPEPTIDE MIMETICS

The design and synthesis of conformationally constrained, non-peptide templates (3-substituted pyrrolidines) which allow the incorporation o f two adjacent amino acid side-chains in an orientation similar to tha t found in the i+1 and i+2 positions of a beta-turn are reported. The NK2 tachykinin receptor affinity of a Trp-Phe mimetic (7a) which mimic s the beta-turn in MEN10627 (8), a constrained cyclic hexapeptide, hig h affinity NK2 tachykinin receptor antagonist, was determined and show n to have no significant binding affinity (NK2, IC50 > 10,000 nM).