PNA-DNA chimeras containing 5-alkynyl-pyrimidine PNA units. Synthesis, binding properties, and enzymatic stability.

Three chimeric dimer synthons (oeg_t(NH)T, oeg_up(NH)T and oeg_uh(NH)T) containing thymine (t), 5-(1-propynyl)-uracil (up) and 5-(1-hexyn-1-yl)-uracil (uh) PNA units with N-(2-hydroxyethyl)glycine (oeg) backbone were synthesized in solution and incorporated into T20 oligonucleotide analogues, using standard P-amidite chemistry. Insertion of dimer blocks led to destabilization of duplexes with dA20 target. The smallest Tm drops were found for chimeras containing oeg_up(NH)T dimers.

Synthesis, biophysical, and biochemical properties of PNA-DNA chimeras.

Three PNA-DNA chimeric dimer synthons (tT, upT and uhT, see Sch. 1) have been synthesized in solution and used to make T20-analogue chimeras applying standard solid-phase DNA synthesis protocol. Duplex forming ability of chimeras with dA20 and their hydrolyses by 3'- and 5'-exonucleases (snake venom and bovine spleen phosphodiesterase, respectively) have been investigated.

Synthesis and enzymatic characterization of P1-thio-P2-oxo trideoxynucleoside diphosphates having AZT, FdU, or dT at the 3'-position.

Model compounds for oligonucleotide-prodrugs, P1-thio-P2-oxo-trideoxyribonucleoside diphosphates: d[G(s)C(o)X] and d[T(s)A(o)X] (X = AZT, FdU or dT) have been prepared, and their hydrolyses by snake venom phosphodiesterase and nuclease S1 are described.

Comparison of the toxicity of fluconazole and other azole antifungal drugs to murine and human granulocyte-macrophage progenitor cells in vitro.

We studied the inhibitory effects on colony formation by granulocyte-macrophage colony forming units (cfu-gm) of eight azole antifungal agents in vitro. All agents, except fluconazole, inhibited colony formation dose-dependently with 50% inhibitory concentrations (IC50) in the range of 0.78-49 micromol/L in cultures of murine and human bone marrow.

Central benzodiazepine receptors: in vitro efficacies and potencies of 3-substituted 1,4-benzodiazepine stereoisomers.

3-Acyloxy-, 3-methoxy-, and 3-alkyl-substituted derivatives of the benzodiazepine (BZ) agonist desmethyl-diazepam (DMD) were resolved, and the stereochemical properties of binding to central BZ receptors were investigated in synaptosomal membrane preparations of rat brain. Decreasing potency and stereoselectivity of 3-methyl, 3-ethyl, and 3-isopropyl derivatives in displacement of [3H]diazepam binding can be attributed to differential susceptibilities for steric hindrance of 3-axial versus 3-equatorial substituents of the binding conformation M. Chirality in the alpha-methyl-beta-phenyl-propionic acyl moiety of oxazepam, the 3-OH-derivative of DMD, was noncritical in binding, whereas the beta-phenyl substituent selectively increased the binding of the 3S-stereoisomer.