F. Debart et al., ANOMERIC INVERSION (FROM BETA TO ALPHA) IN METHYLPHOSPHONATE OLIGONUCLEOSIDES ENHANCES THEIR AFFINITY FOR DNA AND RNA, Nucleic acids research, 26(20), 1998, pp. 4551-4556
Here we report that the poor binding of methylphosphonate oligodeoxynu
cleosides (MP-ODNs) to their nucleic acid targets can be improved by a
dditional inversion of the anomeric configuration (from beta to alpha)
in the sugar moieties to give a new class of analogs, MP alpha-oligon
ucleosides, MP alpha-dT(12) and MP 5' alpha-d(TCTTAA-CCCACA) 3' were s
ynthesized and their ability to form hybrids with complementary single
stranded (ss)DNA and ssRNA, as well as with double stranded (ds)DNA,
was evaluated. The thermal stability of hybrids formed with MP alpha-a
nalogs was compared with the affinity of phosphodiester (PO) and phosp
horothioate (PS) beta- and alpha-oligomers for their targets. Non-ioni
c MP alpha-oligonucleosides bound to their complementary DNA and RNA s
trands more tightly than their homologues with natural beta-anomeric c
onfiguration did. With DNA target, NIP alpha-oligomers formed duplexes
more stable than the corresponding natural PO beta-oligomer did. MP a
lpha-heteropolymer hybridized to RNA target better than PS beta-oligon
ucleotide did but the hybrid was less stable (Delta T-m -0.5 degrees C
per mod.) than the hybrid formed with the natural PO beta-oligomer. O
nly MP alpha-dT(12) bound to dsDNA target at low salt concentration (0
.1 M NaCl).