it is important to determine whether a candidate molecule is capable of penetrating the plasma-brain barrier indrug discovery and development. the aim of this paper is to establish a predictive model for plasma-brainbarrier penetration using simple descriptors the usefulness of the quantum chemical descriptors, calculated atthe level of the dft and he theories using 6-310* basis set for qsar st...

It is important to determine whether a candidate molecule is capable of penetrating the plasma-brain barrier indrug discovery and development. The aim of this paper is to establish a predictive model for plasma-brainbarrier penetration using simple descriptors The usefulness of the quantum chemical descriptors, calculated atthe level of the DFT and HE theories using 6-310* basis set for QSAR st...

Nucleoside analogues have proven to be a highly successful class of anti-cancer and anti-viral drugs. The therapeutic efficacy of nucleoside analogues is dependent of their intracellular phosphorylation. Two cellular nucleoside kinases, deoxycytidine kinase (dCK) and UMP-CMP kinase (CMK) are critical for phosphorylation of cytidine analogues. These kinases provide two first steps of activation ...

Understanding and optimization of the photophysics fluorescent nucleoside analogues are critical for their applications in probing structure dynamics nucleic acids, studying interactions with ligands biomolecules.

BACKGROUND The optimal antiretroviral treatment for patients who have human immunodeficiency virus (HIV) viremia despite treatment with nucleoside reverse-transcriptase inhibitors (nucleoside analogues) remains uncertain. We studied treatment with regimens that combined two nucleoside analogues, at least one of which was new, with the protease inhibitor nelfinavir, the nonnucleoside reverse-tra...

Novel 2'(β)-methyl-5'-deoxyapiose purine phosphonic acid analogues were designed and synthesized from 2-propanone1,3-diacetate. Condensation successfully proceeded from a glycosyl donor 9 under Vorbrüggen conditions. Condensation of aldehyde 14 with Wittig reagent [(diethoxyphosphinyl)methylidene] triphenylphosphorane gave the desired nucleoside phosphonate analogues 15. Ammonolysis and hydroly...

Recently, 4'C-ethynyl nucleoside analogues have been identified as highly potent agents against HIV-1, including several multidrug-resistant strains. In contrast to most known nucleoside inhibitors 4'C-ethynyl nucleoside analogues possess a 3'-hydroxyl function. Here we show that the 5'O-triphosphate of 4'C-ethynyl thymidine gets readily incorporated into a nascent DNA strand by HIV-1 reverse t...

An easy and efficient strategy to obtain libraries of 5'-phosphodiester and 5'-phosphoramidate monoester nucleoside analogues in a highly pure form has been developed, starting from a new nucleoside based solid support. The nucleoside scaffold has been anchored through a 5'-phosphodiester linkage to Tentagel HL resin, functionalized with a 3-chloro-4-hydroxyphenylacetic linker. The solid phase ...

OBJECTIVES To characterize the effect of hepatitis C virus (HCV) polymerase intrinsic genetic heterogeneity on the inhibitory activity of nucleoside and non-nucleoside HCV polymerase inhibitors. METHODS The sensitivity of genotype (GT) 1 HCV NS5B clinical isolates from treatment-naive patients to nucleoside and non-nucleoside polymerase inhibitors was assessed. The genetic diversity at the po...