Synthesis and physicochemical properties of oligonucleotides built with either<i>α</i>-L or<i>β</i>-L nucleotides units and covalently linked to an acridine derivative

Abstract

Modified deoxynucleosides 2′-deoxy- β-L-uridine, β-L-thymidine, α-L-thymidine, 2′-deoxy-β-L-adenosine and 2′-deoxy-α-L-adenosine were synthesized and assembled as homooligomers, respectively: octa-β-L-deoxyuridylates, octa β-L and α-L-thymidylates and tetra β-L and α-L-deoxyadenylates. These unnatural oligomers were then substituted with an acridine derivative. The binding studies of these modified oligonucleotides with D-ribo- and D-deoxyribopoly nucleotides were carried out by absorption spectros copy. While β-L-d(Up)8m5Acr, β-L-d(Tp)8m5Acr, α;-L- (Tp)8m5Acr, did not interact with poly(rA) and poly(dA), β-L-d(Up)4m5Acr, and α-L-d(Ap)4m5Acr, did form double and triple helices with poly(rU) and poly(dT), respectively. Their stability towards nuclease digestion was studied through comparison with that of octa-β-D thymidylate and tetra β-D-deoxyadenylate covalently linked to an acridine derivative. One endonuclease (nuclease P1 from Penicillium citrinum) and two exonucleases (a 3′-exonuclease from Crotalus durissus venom and a 5′-exonuclease extracted from calf thymus) were employed. β-L- and α-L-oligomers demonstrate a high resistance toward nuclease digestion.