Triple-helix formation by oligonucleotides containing the three bases thymine, cytosine, and guanine
| Autor: | Carine Giovannangeli, N T Thuong, M. Rougee, Claude Hélène, Thérèse Garestier |
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| Rok vydání: | 1992 |
| Předmět: |
Guanine
Base pair Stereochemistry Molecular Sequence Data Biology chemistry.chemical_compound Cytosine Structure-Activity Relationship Furocoumarins Multidisciplinary Base Sequence Oligonucleotide HIV Hydrogen Bonding Thymine Restriction enzyme Cross-Linking Reagents chemistry Biochemistry Oligodeoxyribonucleotides DNA Viral Nucleic Acid Conformation DNA Triple helix Research Article |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America. 89(18) |
| ISSN: | 0027-8424 |
| Popis: | A homopurine-homopyrimidine sequence of human immunodeficiency virus (HIV) proviral DNA was chosen as a target for triple-helix-forming oligonucleotides. An oligonucleotide containing three bases (thymine, cytosine, and guanine) was shown to bind to its target sequence under physiological conditions. This oligonucleotide is bound in a parallel orientation with respect to the homopurine sequence. Thymines recognize A.T base pairs to form T.A.T base triplets and guanines recognize a run of G.C base pairs to form G.G.C base triplets. A single 5-methylcytosine was shown to stabilize the triple helix when incorporated in a stretch of thymines; it recognizes a single G.C base pair in a run of A.T base pairs. These results provide some of the rules required for choosing the more appropriate oligonucleotide sequence to form a triple helix at a homopurine-homopyrimidine sequence of duplex DNA. A psoralen derivative attached to the oligonucleotide containing thymine, 5-methylcytosine, and guanine was shown to photoinduce cross-linking of the two DNA strands at the target sequence in a plasmid containing part of the HIV proviral DNA sequence. Triplex formation and cross-linking were monitored by inhibition of Dra I restriction enzyme cleavage. The present results provide a rational basis for the development of triplex-forming oligonucleotides targeted to specific sequences of the HIV provirus integrated in its host genome. |
| Databáze: | OpenAIRE |
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