Structural Studies of the Interaction between Indole Derivatives and Biologically Important Aromatic Compounds. Part XXIII. Sequence-Dependent Interaction of Acidic Amino Acid with Guanine Base in Tryptophan-Containing Dipeptides: Spectroscopic Studies.

Abstract

As a model study to investigate the sequence dependence of a peptide for the interaction with nucleic acid base, four kinds of tryptophan-containing dipeptides [Trp-Glu, Glu-Trp, Trp-Gly and Gly-Trp] were synthesized, and their abilities in forming the complexes with guanine base were examined by fluorescence and proton nuclear magnetic resonance (1H-NMR) methods. The fluorescence titration of each dipeptide with 7-methylguanosine-5'-phosphate (m7GMP) indicated that although the stacking interaction dominates the binding in each peptide, the carboxyl side chain of Glu plays an additional role in the binding with the base. The effect of Glu residue and its sequence dependence for the interaction was more clearly demonstrated by the 1H-NMR titration. Since the association constants determined from the downfield shift of the guanine NH2 resonance exhibited the same tendency as those from the upfield shift of the guanine N7-methyl protons [Trp-Glu > Trp-Gly >Glu-Trp > Gly-Trp], the close cooperation between the hydrogen bond and stacking interactions was suggested to be important for the tight binding of the peptides to the guanine base. Further, it was suggested that the peptide which contains an aromatic amino acid at the N-terminal side and an acidic one at the C-terminal side has an advantage in forming such a complex.