Sequence-specific DNA binding by a rhodium complex: recognition based on sequence-dependent twistability.
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.
Terbrueggen
R H
RH
Division of Chemistry, California Institute of Technology, Pasadena 91125, USA.
Barton
J K
JK
D001482:Base Composition; D001483:Base Sequence; D001665:Binding Sites; D004247:DNA / Q000737:chemistry* / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism*; D006147:Guanine / Q000031:analogs & derivatives; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D009838:Oligodeoxyribonucleotides / Q000737:chemistry*; D009942:Organometallic Compounds; D010618:Phenanthrolines; D010777:Photochemistry; D011487:Protein Conformation; D012238:Rhodium; D013329:Structure-Activity Relationship
D004268:DNA-Binding Proteins; D009838:Oligodeoxyribonucleotides; D009942:Organometallic Compounds; D010618:Phenanthrolines; C094482:bis(phenanthrenequinonediimine)(4-(guanidylmethyl)-1,10-phenanthroline)rhodium(III); D006147:Guanine; D004247:DNA; D012238:Rhodium; C066856:7-deazaguanine