Secondary structure of peptides, 11. How to synthesize helical poly(L‐phenylalanine)?

Polymerizations of L‐phenylalanine‐ N ‐carobxyanhydride(L‐Phe‐NCA) were conducted under various reaction conditions and the secondary structure of the resulting solid poly(L‐phenylalanine)s was examined by means of 50,3 or 75,4 MHz 13 C NMR CP/MAS spectra. When primary alkylamines were used as initiators only α‐helix contents ≤ 60% were obtained regardless of solvent and temperature. However, a part of the β‐sheet structures was thermodynamically unstable and could be converted into α‐helices by reprecipitation. An α‐helix content > 90% was achieved only when weakly nucleophilic reagents, such as aromatic amines or water, were used as initiators in methylene chloride. A kinetic explanation of these results is discussed. Aprotic bases gave low yields of poly(L‐phenylalanine) and substantial amounts of low molecular weight side products. An α‐helix content ≥ 95%, was achieved when L‐Phe‐NCA was polymerized in pyridine at 100°C. The usefulness of IR spectra for the characterization of the secondary structure of poly(L‐phenylalanine) is discussed.