Triplex formation on DNA targets: how to choose the oligonucleotide. 2008

Pierre Vekhoff, and Alexandre Ceccaldi, and David Polverari, and Jean Pylouster, and Claudio Pisano, and Paola B Arimondo
UMR 5153 CNRS, Museum National d'Histoire Naturelle USM0503, 43 rue Cuvier, 75231 Paris cedex 05, France.

Triplex-forming oligonucleotides (TFOs) are sequence-specific DNA binders. TFOs provide a tool for controlling gene expression or, when attached to an appropriate chemical reagent, for directing DNA damage. Here, we report a set of rules for predicting the best out of five different triple-helical binding motifs (TM, UM, GA, GT, and GU, where M is 5-methyldeoxycytidine and U is deoxyuridine) by taking into consideration the sequence composition of the underlying duplex target. We tested 11 different triplex targets present in genes having an oncogenic role. The rules have predictive power and are very useful in the design of TFOs for antigene applications. Briefly, we retained motifs GU and TM, and when they do form a triplex, TFOs containing G and U are preferred over those containing T and M. In the case of the G-rich TFOs, triplex formation is principally dependent on the percentage of G and the length of the TFO. In the case of the pyrimidine motif, replacement of T with U is destabilizing; triplex formation is dependent on the percentage of T and destabilized by the presence of several contiguous M residues. An equation to choose between a GU and TM motif is given.

UI MeSH Term Description Entries
D009369 Neoplasms New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms. Benign Neoplasm,Cancer,Malignant Neoplasm,Tumor,Tumors,Benign Neoplasms,Malignancy,Malignant Neoplasms,Neoplasia,Neoplasm,Neoplasms, Benign,Cancers,Malignancies,Neoplasias,Neoplasm, Benign,Neoplasm, Malignant,Neoplasms, Malignant
D009690 Nucleic Acid Conformation The spatial arrangement of the atoms of a nucleic acid or polynucleotide that results in its characteristic 3-dimensional shape. DNA Conformation,RNA Conformation,Conformation, DNA,Conformation, Nucleic Acid,Conformation, RNA,Conformations, DNA,Conformations, Nucleic Acid,Conformations, RNA,DNA Conformations,Nucleic Acid Conformations,RNA Conformations
D009691 Nucleic Acid Denaturation Disruption of the secondary structure of nucleic acids by heat, extreme pH or chemical treatment. Double strand DNA is "melted" by dissociation of the non-covalent hydrogen bonds and hydrophobic interactions. Denatured DNA appears to be a single-stranded flexible structure. The effects of denaturation on RNA are similar though less pronounced and largely reversible. DNA Denaturation,DNA Melting,RNA Denaturation,Acid Denaturation, Nucleic,Denaturation, DNA,Denaturation, Nucleic Acid,Denaturation, RNA,Nucleic Acid Denaturations
D009838 Oligodeoxyribonucleotides A group of deoxyribonucleotides (up to 12) in which the phosphate residues of each deoxyribonucleotide act as bridges in forming diester linkages between the deoxyribose moieties. Oligodeoxynucleotide,Oligodeoxyribonucleotide,Oligodeoxynucleotides
D003841 Deoxycytidine A nucleoside component of DNA composed of CYTOSINE and DEOXYRIBOSE. Cytosine Deoxyribonucleoside,Cytosine Deoxyriboside,Deoxyribonucleoside, Cytosine,Deoxyriboside, Cytosine
D004247 DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA, Double-Stranded,Deoxyribonucleic Acid,ds-DNA,DNA, Double Stranded,Double-Stranded DNA,ds DNA
D006863 Hydrogen-Ion Concentration The normality of a solution with respect to HYDROGEN ions; H+. It is related to acidity measurements in most cases by pH pH,Concentration, Hydrogen-Ion,Concentrations, Hydrogen-Ion,Hydrogen Ion Concentration,Hydrogen-Ion Concentrations
D001483 Base Sequence The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence. DNA Sequence,Nucleotide Sequence,RNA Sequence,DNA Sequences,Base Sequences,Nucleotide Sequences,RNA Sequences,Sequence, Base,Sequence, DNA,Sequence, Nucleotide,Sequence, RNA,Sequences, Base,Sequences, DNA,Sequences, Nucleotide,Sequences, RNA
D013056 Spectrophotometry, Ultraviolet Determination of the spectra of ultraviolet absorption by specific molecules in gases or liquids, for example Cl2, SO2, NO2, CS2, ozone, mercury vapor, and various unsaturated compounds. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed) Ultraviolet Spectrophotometry
D015536 Down-Regulation A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins. Receptor Down-Regulation,Down-Regulation (Physiology),Downregulation,Down Regulation,Down-Regulation, Receptor

Related Publications

Pierre Vekhoff, and Alexandre Ceccaldi, and David Polverari, and Jean Pylouster, and Claudio Pisano, and Paola B Arimondo
January 2008, Nucleic acids symposium series (2004),
Pierre Vekhoff, and Alexandre Ceccaldi, and David Polverari, and Jean Pylouster, and Claudio Pisano, and Paola B Arimondo
March 1993, Journal of molecular biology,
Pierre Vekhoff, and Alexandre Ceccaldi, and David Polverari, and Jean Pylouster, and Claudio Pisano, and Paola B Arimondo
November 2007, Chembiochem : a European journal of chemical biology,
Pierre Vekhoff, and Alexandre Ceccaldi, and David Polverari, and Jean Pylouster, and Claudio Pisano, and Paola B Arimondo
January 2007, Nucleic acids symposium series (2004),
Pierre Vekhoff, and Alexandre Ceccaldi, and David Polverari, and Jean Pylouster, and Claudio Pisano, and Paola B Arimondo
October 2007, Nature genetics,
Pierre Vekhoff, and Alexandre Ceccaldi, and David Polverari, and Jean Pylouster, and Claudio Pisano, and Paola B Arimondo
April 2012, Biochimie,
Pierre Vekhoff, and Alexandre Ceccaldi, and David Polverari, and Jean Pylouster, and Claudio Pisano, and Paola B Arimondo
January 2000, Nucleic acids symposium series,
Pierre Vekhoff, and Alexandre Ceccaldi, and David Polverari, and Jean Pylouster, and Claudio Pisano, and Paola B Arimondo
January 2007, Nucleosides, nucleotides & nucleic acids,
Pierre Vekhoff, and Alexandre Ceccaldi, and David Polverari, and Jean Pylouster, and Claudio Pisano, and Paola B Arimondo
June 2010, Bioconjugate chemistry,
Pierre Vekhoff, and Alexandre Ceccaldi, and David Polverari, and Jean Pylouster, and Claudio Pisano, and Paola B Arimondo
January 2012, Nucleosides, nucleotides & nucleic acids,
Copied contents to your clipboard!