Sequence-selective DNA recognition and photocleavage: a comparison of enantiomers of Rh(en)2phi3+.
The recognition and photoinduced cleavage of DNA by the enantiomers of bis(ethylenediamine)-(9,10-phenanthrenequinone diimine)Rh(III) [Rh(en)2phi3+] have been characterized and the basis for enantioselective differences delineated. Rh(en)2phi3+ isomers bind strongly to DNA via intercalation and, upon photoactivation with near-UV light, produce direct strand cleavage. On the basis of product analysis, the photoinduced DNA cleavage appears to proceed by a mechanism consistent with that observed for the parent Rh(phen)2phi3+, involving direct abstraction of the 3'-hydrogen atom of the deoxyribose by the activated, intercalated phi. Quantitative photocleavage titrations indicate tight binding by both enantiomers to the DNA duplex. For delta-Rh(en)2phi3+, DNA site affinities range from 0.3 x 10(6) to 8.0 x 10(6) M-1, and a distinct preference for GC sites is evident. lambda-Rh(en)2phi3+ is found to be sequence neutral with an average site affinity of 2 x 10(6) M-1. The basis for sequence selectivity of the enantiomers has been examined through comparison of photocleavage patterns to those of several phi complexes of rhodium(III) containing or lacking axial amines; those complexes containing the axial amines are found to target GC sites. DNA photocleavage studies on oligonucleotides containing the modified bases O6-methylguanine, 7-deazaguanine, and deoxyuracil have been utilized to determine points of interaction on the DNA helix. These results establish binding by both complexes in the major groove of DNA. Differences in site recognition between enantiomers are attributed to the different hydrogen bonding and van der Waals contacts available in the major groove for the ancillary ethylenediamine ligands which differ in disposition in the two isomers.
Shields
T P
TP
Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena 91125, USA.
Barton
J K
JK
D001483:Base Sequence; D001665:Binding Sites; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D003856:Deoxyuracil Nucleotides / Q000378:metabolism; D003959:Diamines / Q000737:chemistry* / Q000378:metabolism*; D005029:Ethylenediamines; D006147:Guanine / Q000031:analogs & derivatives / Q000378:metabolism; D006860:Hydrogen Bonding; D007364:Intercalating Agents / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009838:Oligodeoxyribonucleotides / Q000737:chemistry / Q000378:metabolism; D009942:Organometallic Compounds / Q000737:chemistry* / Q000378:metabolism*; D010782:Photolysis; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014466:Ultraviolet Rays
D003856:Deoxyuracil Nucleotides; D003959:Diamines; D005029:Ethylenediamines; D007364:Intercalating Agents; D009838:Oligodeoxyribonucleotides; D009942:Organometallic Compounds; C096872:bis(ethylenediamine)(9,10-phenanthrenequinonediamine)rhodium(III); D006147:Guanine; D004247:DNA; C008449:O-(6)-methylguanine; C066856:7-deazaguanine