Synthesis and properties of chemotactic peptide analogs: II. HCO‐Met‐Leu‐Phe‐OMe analogs containing cyclic α,α‐disubstituted amino acids as Met and Phe mimicking residues

As a part of a research program aimed at studying structure activity relationship in the field of chemotactic peptides, modified analogs of the potent chemoattractant HCO‐Met‐Leu‐Phe‐OH (fMLP) of the general formula HCO‐Xaa‐Leu‐Yaa‐OMe are examined. 4‐Aminotetrahydrothiopyran‐4‐carboxylic acid (Thp) and 2‐aminoindane‐2‐carboxylic acid (Ain) have been chosen as achiral, conformationally restricted amino acids suitable to mimick the external Met and Phe residues of fMLP‐OMe. Studies on a first model, namely [Ain3]fMLP‐OMe 1, have already been reported (12). Here the two remaining analogs (Thp1, Ain3) 2 and [Thp1] 3 have been synthesized. The conformation in the crystal of the disubstituted analog 2 has been determined and compared with those adopted by the parent fMLP‐OMe and by previously studied models. The backbone conformation of 2 is characterized by helical folding centred at each of the three residues with the central Leu presenting helical handedness opposite to those of the two ...