Abstract
A four-ring tripeptide containing alternating imidazole and pyrrole carboxamides specifically binds six-base pair 5'-(A,T)GCGC(A,T)-3' sites in the minor groove of DNA. The designed peptide has a specificity completely reversed from that of the tripyrrole distamycin, which binds A,T sequences. Structural studies with nuclear magnetic resonance revealed that two peptides bound side-by-side and in an antiparallel orientation in the minor groove. Each of the four imidazoles in the 2:1 ligand-DNA complex recognized a specific guanine amino group in the GCGC core through a hydrogen bond. Targeting a designated four-base pair G.C tract by this synthetic ligand supports the generality of the 2:1 peptide-DNA motif for sequence-specific minor groove recognition of DNA.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Base Composition
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Base Sequence
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Computer Graphics
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DNA / chemistry
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DNA / metabolism*
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Drug Design
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Hydrogen Bonding
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Imidazoles / chemical synthesis
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Imidazoles / chemistry*
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Imidazoles / metabolism
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Ligands
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Magnetic Resonance Spectroscopy
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Models, Molecular
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Molecular Sequence Data
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Nucleic Acid Conformation
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Oligodeoxyribonucleotides / chemistry
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Oligodeoxyribonucleotides / metabolism
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Oligopeptides / chemical synthesis
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Oligopeptides / chemistry*
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Oligopeptides / metabolism
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Protein Conformation
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Pyrroles / chemical synthesis
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Pyrroles / chemistry*
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Pyrroles / metabolism
Substances
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ImPImP
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Imidazoles
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Ligands
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Oligodeoxyribonucleotides
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Oligopeptides
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Pyrroles
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DNA