Open AccessΑ-DNA II. Synthesis of unnatural Α-anomeric oligodeoxyribonucleotides containing the four usual bases and study of their substrate activities for nucleases
Author(s) -
François Morvan,
Bernard Rayner,
Jean−Louis Imbach,
Sophie Thenet,
Jean-Rémi Bertrand,
Jacques Paoletti,
Claude Malvy,
Claude Paoletti
Publication year - 1987
Publication title -
nucleic acids research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 9.008
H-Index - 537
eISSN - 1362-4954
pISSN - 0305-1048
DOI - 10.1093/nar/15.8.3421
Subject(s) - anomer , oligonucleotide , deoxyribonucleosides , guanine , nucleobase , stereochemistry , uracil , cytosine , nucleoside , pyrimidine , glycosylation , dna , substrate (aquarium) , biology , nucleotide , alpha (finance) , biochemistry , chemistry , gene , medicine , ecology , construct validity , nursing , patient satisfaction
This paper describes for the first time the synthesis of alpha-oligonucleotides containing the four usual bases. Two unnatural hexadeoxyribonucleotides: alpha-[d(CpApTpGpCpG)] and alpha-[d(CpGpCpApTpG)], consisting only of alpha-anomeric nucleotide units, were obtained by an improved phosphotriester method, in solution. Starting material was the four base-protected alpha-deoxyribonucleosides 3a-d. Pyrimidine alpha-deoxynucleosides 3a and 3b were prepared by self-anomerization reactions followed by selective deprotection of sugar hydroxyles, while the two purine alpha-deoxynucleosides 3c and 3d were prepared by glycosylation reactions. In the case of guanine alpha-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 hexadeoxynucleotide alpha-[d(CpApTpGpCpG)] was tested as substrate of selected endo- and exonucleases. In conditions where the natural corresponding beta-hexamer was completely degradated by nuclease S1 and calf spleen phosphodiesterase, the alpha-oligonucleotide remained almost intact.