SOLUTION STRUCTURE OF A PURINE PURINE PYRIMIDINE DNA TRIPLER CONTAINING G-CENTER-DOT-GC AND T-CENTER-DOT-AT TRIPLES

被引:135
作者
RADHAKRISHNAN, I
PATEL, DJ
机构
[1] MEM SLOAN KETTERING CANC CTR,CELLULAR BIOCHEM & BIOPHYS PROGRAM,NEW YORK,NY 10021
[2] COLUMBIA UNIV,COLL PHYSICIANS & SURGEONS,DEPT BIOCHEM & MOLEC BIOPHYS,NEW YORK,NY 10032
关键词
NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; PURINE PURINE PYRIMIDINE DNA TRIPLE HELIX; SOLUTION STRUCTURE;
D O I
10.1016/0969-2126(93)90028-F
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Background: Oligonucleotide-directed triple helix formation allows sequence-specific recognition of double helical DNA. This powerful approach has been used to inhibit gene transcription in vitro and to mediate single sire specific cleavage of a human chromosome. Results: Using a combined NMR and molecular dynamics approach (including relaxation matrix refinement), we have determined the solution structure of an intramolecular purine-purine-pyrimidine (R.RY) DNA tripler containing guanines and thymines in the third strand to high resolution. Our studies define the G.GC and T.AT base triple pairing alignments in the R.RY tripler and identify the structural discontinuities in the third strand associated with the non-isomorphism of the base triples. The 5'-d(TpG)-3' base steps exhibit a pronounced increase in axial rise and reduction in helical twist, while the reverse is observed to a lesser extent, at 5'-d(GpT)-3' steps. A third groove is formed bem een the purine-rich third strand and the pyrimidine strand. It is wider and deeper than the other two grooves. Conclusions: Our structure of the R.RY DNA triplex will be important in the design of oligonucleotide probes with enhanced specificity and affinity for targeting in the genome. The third groove presents a potential target for binding additional ligands.
引用
收藏
页码:135 / 152
页数:18
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