Α-DNA II. Synthesis of unnatural Α-anomeric oligodeoxyribonucleotides containing the four usual bases and study of their substrate activities for nucleases

Abstract

This paper describes for the first time the synthesis of α-oligonucleotides containing the four usual bases. Two unnatural hexadeoxyribonucleotidesi α-[d(CPAPTPGPCPG)] and α-[d(CPGPCPHPTPG)], consisting only of a-anomeric nucleotide units, were obtained by an improved phosphotriester method, in solution. Starting material was the four base-protected α-deoxyribo-nucleosides 3-d. Pyrimidine a-deoxynucleosides 3a and 3b were prepared by self-anomerization reactions followed by selective deprotection of sugar hydroxyles, while the two purine α-deoxynucleosides 3c and 3d were prepared by glycosylation reactions. In the case of guanine α-nucleoside derivative a supplementary base-protecting group: N, N-diphenylcarbamoyl was introduced on O⁶-position in order to avoid side-reactions during oligonucleotide assembling. The hexadeorynucleotide α-[d(CPAPTPGPCPG)] was tested as substrate of selected endo- and exonucleases. In conditions where the natural corresponding β-hexamer was completely degradated by nuclease s1 and calf spleen phosphodiesterase, the α-oligonucleotide remained almost intact.