Hybrid characteristics of oligonucleotides consisting of isonucleoside 2',5'-anhydro-3'-deoxy-3'-(thymin-1-yl)-D-mannitol with different linkage modes.

Oligonucleotides consisting of the isonucleoside repeating unit 2',5'-anhydro-3'-deoxy-3'-(thymin-1-yl)-D-mannitol (4) were synthesized with the monomeric unit 4 incorporated into oligonucleotides as 1'-->4' linkage 4a (oligomer I) or 6'-->4' linkage 4b (oligomer II). The hybrid properties of the two oligonucleotides I and II with their complementary strands were investigated by thermal denaturation and CD spectra. Oligonucleotide I (4a) formed a stable duplex with d(A)(14) with a slightly reduced T(m) value of 36.6 degrees C, relative to 38.2 degrees C for the control duplex d(T)(14)/d(A)(14), but oligomer II (4b) failed to hybridize with a DNA complementary single strand. The spectrum of the duplex oligomer I/d(A)(14) showed a positive CD band at 217 nm and a negative CD band at 248 nm attributable to a B-like conformation. Molecular modeling showed that in the case of oligomer I: the C6' hydroxy group of each unit could be located in the groove area when hybridized to the DNA single strand, which might contribute additional hydrogen bonding to the stability of duplex formation.

Synthesis of lactosyl phosphate diester derivatives of nucleosides.

Derivatives of the lactosyl phosphate diester and the lactosyl thiophosphate diester of 1-(beta-D-arabinofuranosyl)cytosine (Ara-C) and 9-(beta-D-arabinofuranosyl)adenine (Ara-A) were synthesized by condensation of 3-hydroxypropyl lactoside and a protected Ara-C or Ara-A via H-phosphonate methodology and phosphoramidite methodology, respectively.

[Synthesis of analogues of carbocyclic nucleoside].

The derivatives of 5'-dehydroxymethyl carbocyclic nucleoside were synthesized by condensation of cyclopentenyl chloride and corresponding pyrimidines followed by epoxidation and substitution. All compounds were screened for anticancer and antiviral activities and no activity was found.