Sequence-Specific DNA Binding by a Rhodium Complex: Recognition Based on Sequence-Dependent Twistability
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, A-1-Rh(MGP)_2phi^(5+). This metallointercalator, containing pendant guanidinium groups, binds in the major groove of DNA at subnanomolar concentrations to the 6 base pair sequence 5'-CAT A TG-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° 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.
Additional Information
© 1995 American Chemical Society. Received March 22, 1995. Publication Date: July 1995. This work has been supported by the NIH (GM33309), which we gratefully acknowledge.Additional details
- Eprint ID
- 65941
- Resolver ID
- CaltechAUTHORS:20160405-140026640
- NIH
- GM33309
- Created
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2016-04-06Created from EPrint's datestamp field
- Updated
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2021-11-10Created from EPrint's last_modified field