K. Pongracz et Sm. Gryaznov, ALPHA-OLIGODEOXYRIBONUCLEOTIDE N3'-]P5' PHOSPHORAMIDATES - SYNTHESIS AND DUPLEX FORMATION, Nucleic acids research, 26(4), 1998, pp. 1099-1106
The synthesis and hybridization properties of novel nucleic acid analo
gs, alpha-anomeric oligodeoxyribonucleotide N3'-->P5' phosphoramidates
, are described, The alpha-3'-aminonucleoside building blocks used for
oligonucleotide synthesis were synthesized from 3'-azido-3'-deoxythym
idine or 3'-azido-2',3'-dideoxyuridine via acid catalyzed anomerizatio
n or transglycosylation reactions, The base-protected alpha-5'-O-DMT-3
'-aminonucleosides were assembled into dimers and oligonucleotides on
a solid support using the oxidative phosphorylation method, H-1 NMR an
alysis of the alpha-N3'-->P5' phosphoramidate dimer structures indicat
es significant differences in the sugar puckering of these compounds r
elative to the beta-N3'-->P5' phosphoramidates and to the alpha-phosph
odiester counterparts, Additionally, the ability of the alpha-oligonuc
leotide N3'-->P5' phosphoramidates to form duplexes was studied using
thermal denaturation experiments, Thus the N3'-->P5' phosphoramidate d
ecamer containing only alpha-thymidine residues did not bind to poly(A
) and exhibited lower duplex thermal stability with poly(dA) than that
for the corresponding beta-anomeric phosphoramidate counterpart, A mi
xed base decamer alpha-CTTCTTCCTT formed duplexes with the RNA and DNA
complementary strands only in a parallel orientation. Melting tempera
tures of these complexes were significantly lower, by 34-47 or 15-25 d
egrees C, than for the duplexes formed by the isosequential beta-phosp
horamidates in antiparallel and parallel orientations respectively, In
contrast, the alpha-decaadenylic N3'-->P5' phosphoramidate formed dup
lexes with both RNA and DNA complementary strands with a stability sim
ilar to that of the corresponding beta-anomeric phosphoramidate, Moreo
ver, the self-complementary oligonucleotide alpha-ATATATATAT did not f
orm an alpha:alpha homoduplex, These results demonstrate the effects o
f 3'-aminonucleoside anomeric configuration on sugar puckering and con
sequently on stability of the duplexes.