Sequence-specific DNA binding by a rhodium complex: recognition based on sequence-dependent twistability.

R H Terbrueggen; J K Barton

doi:10.1021/bi00026a003

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Sequence-specific DNA binding by a rhodium complex: recognition based on sequence-dependent twistability.

R H Terbrueggen·J K Barton

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Abstract

The chemical construction of small molecules targeted to DNA depends upon the sequence-dependent structure of the double helix. Here we describe a new structural element to be considered in the sequence-specific recognition of DNA, sequence-dependent DNA twistability. The importance of sequence-dependent DNA twistability is demonstrated in the DNA recognition properties of a novel synthetic rhodium intercalator, lambda-1-Rh(MGP)2phi5+. This metallointercalator, containing pendant guanidinium groups, binds in the major groove of DNA at subnanomolar concentrations to the 6 base pair sequence 5'-CATATG-3' with enantiospecificity. An essential feature of this recognition is the sequence-specific unwinding of the DNA helix, which permits direct contacts between guanidinium functionalities on the metal complex and guanine residues. Through an assay developed to test for sequence-specific DNA unwinding, a 70 +/- 10 degrees unwinding of the sequence 5'-CATATG-3' is established with specific binding by the metal complex. This sequence-dependent twistability may be an essential feature of the recognition of sequences by DNA-binding proteins and may be exploited in future design.

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Base Composition Base Sequence Binding Sites DNA DNA-Binding Proteins Guanine Models, Molecular Molecular Sequence Data Nucleic Acid Conformation Oligodeoxyribonucleotides Organometallic Compounds Phenanthrolines Photochemistry Protein Conformation Rhodium Structure-Activity Relationship Comparative Study Journal Article Research Support, U.S. Gov't, P.H.S.

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R H Terbrueggen, J K Barton. 1995-07-04. Sequence-specific DNA binding by a rhodium complex: recognition based on sequence-dependent twistability.. https://doi.org/10.1021/bi00026a003

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