Synthesis and properties of alternating poly(Lys‐Phe) and comparison with the random copolymer poly(Lys⁵¹, Phe⁴⁹)

Abstract The alternating copolypeptide poly(Lys‐Phe) was obtained by synthesis and polymerization of the respective tetrapeptide. Conformation and conformational transitions in aqueous solutions and in water–organic solvent mixtures were determined and compared with those of the random copolymer poly(Lys 51 ,Phe 49 ) by circular dichroism measurements. The alternating copolymer reveals a very strong tendency to adopt the β structure, which is accomplished by raising the pH or by adding sodium perchlorate or methanol. Partial α‐helical conformation, however, is obtained in the presence of 10–20% of the strong helix‐forming solvent hexafluoroisopropanol. The random copolymer reveals a much weaker preference for the β structure. It assumes the α helix in mixtures of water with hexafluoroisopropanol and also in those with methanol. As was already reported by Peggion et al. and confirmed by the present work, the addition of sodium perchlorate also leads to the helix conformation [(1972) Biopolymers 11 , 633], whereas β structure is obtained by raising the pH [(1970) Macromolecules 3 , 194]. These studies reveal the significance of affinities determined by near neighbor interactions in polypeptides.