Solution structure of a purine·purine·pyrimidine DNA triplex containing G·GC and T·AT triples Journal Article
| Authors: | Radhakrishnan, I.; Patel, D. J. |
| Article Title: | Solution structure of a purine·purine·pyrimidine DNA triplex containing G·GC and T·AT triples |
| Abstract: | 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 site 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 triplex 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 triplex 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 between 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. © 1993. |
| Keywords: | comparative study; molecular genetics; methodology; pyrimidines; chemistry; dna; molecular sequence data; guanine; nucleotide sequence; magnetic resonance spectroscopy; nuclear magnetic resonance spectroscopy; base sequence; hydrogen bond; hydrogen bonding; models, molecular; purines; chemical structure; purine derivative; conformation; nucleic acid conformation; pyrimidine derivative; computer graphics; pyrimidine; macromolecule; adenine; oligodeoxyribonucleotides; thymine; cytosine; base composition; article; oligodeoxyribonucleotide; support, u.s. gov't, p.h.s.; support, u.s. gov't, non-p.h.s.; macromolecular systems; solution structure; dna base composition; purine·purine·pyrimidine dna triple helix |
| Journal Title: | Structure |
| Volume: | 1 |
| Issue: | 2 |
| ISSN: | 0969-2126 |
| Publisher: | Cell Press |
| Date Published: | 1993-10-15 |
| Start Page: | 135 |
| End Page: | 152 |
| Language: | English |
| DOI: | 10.1016/0969-2126(93)90028-f |
| PUBMED: | 8069626 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 March 2019 -- Source: Scopus |
