Antiparallel side-by-side dimeric motif for sequence-specific recognition in the minor groove of DNA by the designed peptide 1-methylimidazole-2-carboxamide netropsin.
The designed peptide 1-methylimidazole-2-carboxamide netropsin (2-ImN) binds specifically to the sequence 5'-TGACT-3'. Direct evidence from NMR spectroscopy is presented that this synthetic ligand binds DNA as a 2:1 complex, which reveals that the structure is an antiparallel dimer in the minor groove of DNA. This is in contrast to the 1:1 complexes usually seen with most crescent-shaped minor groove binding molecules targeted toward A+T-rich tracts but reminiscent of a dimeric motif found for distamycin at high concentrations. These results suggest that sequence-dependent groove width may play an important role in allowing an expanded set of DNA binding motifs for synthetic peptides.
Mrksich
M
M
Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena 91125.
Wade
W S
WS
Dwyer
T J
TJ
Geierstanger
B H
BH
Wemmer
D E
DE
Dervan
P B
PB
D001483:Base Sequence; D001665:Binding Sites; D004247:DNA / Q000737:chemistry*; D006860:Hydrogen Bonding; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009429:Netropsin / Q000031:analogs & derivatives* / Q000737:chemistry; D009690:Nucleic Acid Conformation; D009838:Oligodeoxyribonucleotides / Q000737:chemistry*; D011487:Protein Conformation
D008024:Ligands; D009838:Oligodeoxyribonucleotides; C076037:1-methylimidazole-2-carboxamide netropsin; D009429:Netropsin; D004247:DNA