Partial intercalation with nucleic acids of peptides containing aromatic and basic amino acids

Abstract

A series of oligopeptides containing aromatic and basic residues were synthesized and their interactions with double-stranded nucleic acids studied by proton and phosphorus NMR, viscometry, and DNA melting temperature (T_m). The oligopeptides prepared contain two aromatic amino acids (phenylalanine or p-nitrophenylalanine) as well as one or two lysyl residues. The nucleic acids studied were calf thymus DNA, poly(dA-dT)₂, poly(dA) · poly(dT), poly(dG-dC)₂, poly(dG) · poly(dC), and d(ATGCAT)₂. The results obtained show stacking of both aromatic residues of the oligopeptides with the nucleic acids. Higher upfield shifts of the aromatic amino acid residues were always observed with alternating nucleic acids and were higher with poly(dA-dT)₂ in all cases. Evidence for two types of complexes of Lys-Phe-Gly-Gly-p-NO₂Phe-LysNH₂ with DNA was obtained by NMR, one attributed to a purely electrostatic complex and another involving stacking interactions. Studies with d(ATGCAT)₂ indicate that the aromatic residues of the oligopeptides were stacked with the terminal AT base pairs preferentially binding at the ends of the hexanucleotide. © 1999 John Wiley & Sons, Inc. Biospectroscopy 5: 313–322, 1999