title: Side-chain cross-linked short α-helices that behave like original proteins in biomacromolecular interactions.
abstract: We explored the effect of α-helical stabilization upon the binding of short peptides to DNAs. The short peptides were designed according to the binding domains of DNA-binding proteins and were cross-linked between their side chains with diacetylenic or isophthalic cross-linking agents to keep stable α-helices. The binding abilities of the peptides to DNAs were evaluated by fluorescence resonance energy transfer analysis. When a cross-linked peptide based on the homeodomain of the transcription factor was titrated with a target DNA duplex, its dissociation constant (Kd) was calculated to be ~0.5 nM. This value was the double-digit smaller than that of the corresponding non-cross-linked peptide. The cross-linked peptide showed high substrate specificity for DNAs at the same level as the original DNA-binding protein.
authors.affiliation: Graduate School of Pharmaceutical Sciences, University of Toyama, Sugitani 2630, Toyama 930-0194, Japan.
authors.forename: Masaoki
authors.initials: M
authors.lastname: Kajino
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Fujimoto
authors.forename: Masahiko
authors.initials: M
authors.lastname: Inouye
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D003432:Cross-Linking Reagents / Q000494:pharmacology*; D004247:DNA / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism*; D051543:Hepatocyte Nuclear Factor 3-gamma / Q000737:chemistry / Q000378:metabolism; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D055550:Protein Stability; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary
chemical_list: D003432:Cross-Linking Reagents; D004268:DNA-Binding Proteins; D010446:Peptide Fragments; D051543:Hepatocyte Nuclear Factor 3-gamma; D004247:DNA