Synthetic alpha-helical peptides incorporating intercalators for DNA recognition.
The design and synthesis of a water-soluble 14-residue peptide, in which a quinoline intercalator is attached to the peptide backbone via alkylation of a central cysteine residue, is reported. 600 MHz 1H NMR spectroscopy and circular dichroism indicate that the peptide forms a nascent helix in aqueous solution, ie. an ensemble of turn-like structures over several adjacent residues in the peptide. A large number of sequential dNN(i, i+1) connectivities were observed in NOESY spectra, and titration of trifluoroethanol into a solution of the peptide resulted in the characteristic CD spectrum expected for an alpha-helix. At low DNA concentrations, CD spectroscopy indicates that this helical conformation is stabilized, presumably due to folding of the peptide in the major groove of DNA.
Brown
C L
CL
Department of Organic Chemistry, University of Sydney, NSW, Australia.
Harding
M M
MM
D000595:Amino Acid Sequence; D002942:Circular Dichroism; D017076:Computer-Aided Design; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D015195:Drug Design; D007364:Intercalating Agents / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D017433:Protein Structure, Secondary
D004268:DNA-Binding Proteins; D007364:Intercalating Agents; D010455:Peptides; D004247:DNA