Chiral and steric effects in the efficient binding of -anomeric deoxyoligonucleoside N-alkylphosphoramidates to ssDNA and RNA
| Autor: | Bernard Rayner, Alain Laurent, Magali Naval, Françoise Debart, Jean-Jacques Vasseur |
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| Přispěvatelé: | Chimie organique biomoléculaire de synthèse (COBS), Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS) |
| Rok vydání: | 1999 |
| Předmět: |
Steric effects
Alkylation Base Pair Mismatch Stereochemistry Base pair Oligonucleotides DNA Single-Stranded Stereoisomerism [CHIM.THER]Chemical Sciences/Medicinal Chemistry Biology Nucleic Acid Denaturation 010402 general chemistry 01 natural sciences chemistry.chemical_compound [CHIM.ANAL]Chemical Sciences/Analytical chemistry Genetics [CHIM]Chemical Sciences Base Pairing Base Sequence [CHIM.ORGA]Chemical Sciences/Organic chemistry 010405 organic chemistry Oligonucleotide Osmolar Concentration Temperature Nucleic Acid Hybridization RNA Phosphorus 0104 chemical sciences Biochemistry chemistry Gene Products tat Phosphodiester bond HIV-1 Thermodynamics tat Gene Products Human Immunodeficiency Virus Chirality (chemistry) DNA Research Article |
| Zdroj: | Nucleic Acids Research Nucleic Acids Research, Oxford University Press, 1999, 27 (21), pp.4151-4159. ⟨10.1093/nar/27.21.4151⟩ |
| ISSN: | 1362-4962 0305-1048 |
| DOI: | 10.1093/nar/27.21.4151 |
| Popis: | International audience; We report hybridization properties of new phosphate-modified α α α α-oligonucleoside analogs with non-ionic or cationic internucleotide linkages such as methoxy-ethylphosphoramidate (PNHME), phosphoromorpholi-date (PMOR) and dimethylaminopropylphosphor-amidate (PNHDMAP). First we evaluated the chirality effect of the phosphorus atom on the affinity of α α α α-or β β β β-dodecanucleoside phosphodiesters containing one chirally enriched N-alkylphosphoramidate linkage located in the middle of the sequence d(TCTT-AA*CCCACA). As for P-substituted β β β β-oligonucleo-tides, a difference in binding behavior between the two diastereoisomers (difference in ∆ ∆ ∆ ∆T m) exists in the hybridization properties of α α α α-analogs when DNA was the target but this effect was not detrimental to duplex stability. This effect was considerably reduced when RNA was the target. Secondly we studied the effect of steric hindrance around phosphorus on the affinity of fully modified β β β β-and α α α α-oligo-nucleoside N-alkylphosphoramidates for their DNA and RNA targets. This effect was very weak with α α α α-analogs whereas it was more pronounced with β β β β-oligos. PNHME-modified α α α α-oligonucleosides formed more stable duplexes with DNA (∆ ∆ ∆ ∆T m +9.6°°°°C) and RNA (∆ ∆ ∆ ∆T m +1.4°°°°C) targets than the 'parent' phosphodiester. Finally, base pairing specificity of these α α α α-oligonucleo-side N-alkylphosphoramidates for their targets was found to be as high as for natural oligonucleoside phosphodiesters. |
| Databáze: | OpenAIRE |
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