SPECIFICITY OF DNA-BASIC POLYPEPTIDE INTERACTIONS .3. SEQUENTIAL AND RANDOM COPOLYMERS OF LYSINE AND AROMATIC AMINO-ACIDS

Sequential and random lysine copolymers containing various amounts of different aromatic amino acids were synthesized. The sequential copolypeptides exhibited strong dependence of yield and degree of polymerization on the amino acid sequence of the repeating unit. To elucidate the specific contributions of aromatic side chains to the interaction of these copolymers with DNA, direct‐mixed complexes were studied by thermal denaturation and CD. The melting behaviour of peptide‐bound DNA was found to be strongly affected by amino acid composition and sequence. The contribution of the different aromatic amino acids to thermal stability decreased in the order: polylysine > [Lys, Tyr]n > [Lys,Phe]n > [Lys,(OMe)Tyr]n. The CD spectrum of DNA was altered by random copolymers, whereas sequential copolymers exhibited no changes. The influence of the random copolymers on the CD spectrum of DNA decreased in the series: polylysine > [Lys,Phe]n > [Lys,(OMe)Tyr]n > [Lys,Tyr]n. The contribution of the different aromatic amino acids to thermal stability is interpreted as stacking tendencies toward denatured and, in the case of Tyr, H‐bond formation with native DNA. The differences found for the random and the sequential polypeptides can best be explained by assuming a cooperative action of rather small peptide segments. Copyright © 1979 John Wiley & Sons, Inc.