TY - JOUR
T1 - Triplex formation by oligonucleotides containing novel deoxycytidine derivatives
AU - Huang, Chin Yi
AU - Bi, Guixia
AU - Miller, Paul S.
N1 - Funding Information:
The authors wish to thank Ms Sarah Kipp for help in synthesizing the oligonucleotides, Dr Tina L.Trapane for help in obtaining the circular dichroism spectra and Dr David Shortle for use of the circular dichroism spectropolarimeter. This research was supported by a grant from the National Institutes of Health (GM45012). NMR studies were performed in the Biochemistry NMR Facility at the Johns Hopkins University, which was established by a grant from the National Institutes of Health (GM27512) and a Biomedical Shared Instrumentation Grant (RR06262). C-YH was a GENTA Inc. post-doctoral fellow in the Department of Biochemistry.
PY - 1996
Y1 - 1996
N2 - Homopurine sequences of duplex DNA are binding sites for triplex-forming oligodeoxyribopyrimidines. The interactions of synthetic duplex DNA targets with an oligodeoxyribopyrimidine containing N4-(6-amino-2-pyridinyl)deoxycytidine (1), a nucleoside designed to interact with a single C·G base pair interruption of the purine target tract, was studied by UV melting, circular dichroism spectroscopy and dimethylsulfate alkylation experiments. Nucleoside 1 supports stable triplex formation at pH 7.0 with formation of a 1·Y·Z triad, where Y·Z is a base pair in the homopurine tract of the target. Selective interaction was observed when Y·Z was C·G, although A·T and, to a lesser extent, T·A and G·C base pairs were also recognized. The circular dichroism spectra of the triplex having a 1·C·G triad were similar to those of a triplex having a C+·G·C triad, suggesting that the overall structures of the two triplexes are quite similar. Removal of the 6-amino group from 1 essentially eliminated triplex formation. Reaction of a triplex having the 1·C·G triad with dimethylsulfate resulted in a 50% reduction of methylation of the G residue of this triad. In contrast, the G of a similar triplex containing a U·C·G triad was not protected from methylation by dimethylsulfate. These results are consistent with a binding mode in which the 6-amino-2-pyridinyl group of 1 spans the major groove of the target duplex at the 1·C·G binding site and forms a hydrogen bond with the O6 of G. An additional stabilizing hydrogen bond could form between the N4 of the imino tautomer of 1 and the N4 amino group of C.
AB - Homopurine sequences of duplex DNA are binding sites for triplex-forming oligodeoxyribopyrimidines. The interactions of synthetic duplex DNA targets with an oligodeoxyribopyrimidine containing N4-(6-amino-2-pyridinyl)deoxycytidine (1), a nucleoside designed to interact with a single C·G base pair interruption of the purine target tract, was studied by UV melting, circular dichroism spectroscopy and dimethylsulfate alkylation experiments. Nucleoside 1 supports stable triplex formation at pH 7.0 with formation of a 1·Y·Z triad, where Y·Z is a base pair in the homopurine tract of the target. Selective interaction was observed when Y·Z was C·G, although A·T and, to a lesser extent, T·A and G·C base pairs were also recognized. The circular dichroism spectra of the triplex having a 1·C·G triad were similar to those of a triplex having a C+·G·C triad, suggesting that the overall structures of the two triplexes are quite similar. Removal of the 6-amino group from 1 essentially eliminated triplex formation. Reaction of a triplex having the 1·C·G triad with dimethylsulfate resulted in a 50% reduction of methylation of the G residue of this triad. In contrast, the G of a similar triplex containing a U·C·G triad was not protected from methylation by dimethylsulfate. These results are consistent with a binding mode in which the 6-amino-2-pyridinyl group of 1 spans the major groove of the target duplex at the 1·C·G binding site and forms a hydrogen bond with the O6 of G. An additional stabilizing hydrogen bond could form between the N4 of the imino tautomer of 1 and the N4 amino group of C.
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U2 - 10.1093/nar/24.13.2606
DO - 10.1093/nar/24.13.2606
M3 - Article
C2 - 8692703
AN - SCOPUS:0029901452
VL - 24
SP - 2606
EP - 2613
JO - Nucleic Acids Research
JF - Nucleic Acids Research
SN - 1362-4962
IS - 13
ER -