Syntheses and binding studies of oligonucleotides containing N-hydroxycarbamate linkages: potential DNA cleaving antisense oligomers

An efficient synthesis of N-hydroxycarbamate containing thymidine dimer 9 w as accomplished and it was incorporated into automatic DNA syntheses to mak e thymidine 16mers T*-1, T*-2 and T*-3. Binding abilities of T*-1, T*-2 and T*-3 with poly (dA)-16mer were assayed by melting denaturation (Tm) studie s of the corresponding duplexes. Iron binding ability of a thymidine oligom er with N-hydroxycarbamate linkages was studied by MALDI-MS. Nuclease stabi lity assays showed that the modified oligonucleotides have enhanced resista nce toward nuclease SI (endonuclease) compared to natural oligonucleotides. (C) 2000 Elsevier Science Ltd. All rights reserved.