Oligothymidylates Comportant La Structure Alternee Alkylphosphotriester-Phosphodiester Et Lies De Facon Covalente A Un Agent Intercalant
- 1 January 1986
- journal article
- research article
- Published by Taylor & Francis in Phosphorus and Sulfur and the Related Elements
- Vol. 26 (1), 63-73
- https://doi.org/10.1080/03086648608084571
Abstract
Four oligothymidylates involving alternating alkylphosphotriester-phosphodiester backbones with the same steric configuration for all the phosphotriester groups [(Tp(R)Tp)2(CH2)5Acr 2bα; 2bβ (R = Et); cα, 2cβ (R = Me3C—CH2)] have been synthesized by the phosphotriester method in solution from each pure α and β isomers of the ethylated 5b or neopentylated 5c dinucleoside. This partial esterification of the phosphate groups stabilizes the nucleic acid chain against nucleolytic attack by P 1 and S 1 nucleases. This effect increases with the size of the alkyl groups. It also depends upon the steric configuration of the alkylphosphotriester groups: the β isomers are more resistant to S 1 nuclease than the a isomers. Tetrathymidylates bearing two “neopentyl” groups (Tp(CH,CMe3)Tp)2 (CH2)5Acr 2cα and 2cβ give specific complexes with poly r(A) and the β isomer 2c binds a little stronger than the tetrahymidylate (Tp)n (CH2)5 Acr. The neopentyl group is stable under the conditions required for the synthesis of oligodeoxynucleotides involving the four nucleic acid bases. It can be used for the partial esterification of the phosphodiester groups. Quatre oligothymidylates comportant la structure alternée alkyl-phosphotriester-phosphodiester et dont tous les groupes alkylphosphotriesters possèdent la měme configuration stérique [(Tp(R)Tp)2 (CH2)5 Acr, 2bα 2bβ (R = Et); 2cα, 2Cβ (R = Me,C—CH2)] ont été synthétisés selon la méthode au phosphotriester en solution à partir de chacun des isomères a et β du dinucleéoide éthylé 5b ou néopentylé 5c. Cette estérification partielle des groupes phosphates augmente la stabilité de la cha[icaron]ne nucléotidique vis-à-vis de l'action des nucléases. Cet effet stabilisateur augmente avec la taille du groupe alkyle (en présence des endonucléases P 1 et S 1) et depend de la configuration stirique des groupes alkylphosphotriesters (en présence de S 1 les isomères β sont plus résistants que les isomères α). Les tétrathymidylates porteurs de deux groupes néopentyle (Tp(CH2CMe3)Tp)2(CH2),Acr 2cα et 2cβ forment des complexes spécifiques avec l'acide polyriboadinylique; le complexe formé à partir de l'isomere 2cβ est légèrement plus stable que celui formé a partir du tètrathymidylate (Tp)4(CH2)5Acr. Le groupe néopentyl est stable dans les conditions de synthèse des oligodéoxynucliotides comportant les quatre bases nucléiques; il peut donc ětre utilisé pour estérifier partiellement les groupes phosphodiesters.Keywords
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