Enzymatic Synthesis of Biologically Active -Phosphinic Analogue of α-Ketoglutarate.

Amino acid analogues with a phosphorus-containing moiety replacing the carboxylic group are promising sources of biologically active compounds. The -phosphinic group, with hydrogen-phosphorus-carbon (H-P-C) bonds and a flattened tetrahedral configuration, is a bioisostere of the carboxylic group. Consequently, amino--phosphinic acids undergo substrate-like enzymatic transformations, leading to new biologically active metabolites.

Asymmetric synthesis of warfarin and its analogs catalyzed by C-symmetric squaramide-based primary diamines.

Novel C2-symmetric N,N'-bis(2-amino-1,2-diphenylethyl)squaramides with 1,2-di(pyridin-2-yl)ethane and 1,2-diphenylethane spacer groups were designed and applied as organocatalysts in asymmetric additions of 4-hydroxycoumarin and 4-hydroxy-6-methyl-2H-pyran-2-one to α,β-unsaturated ketones. Both enantiomers of the anticoagulant warfarin and its analogs were prepared in up to 96% yield and with 96% ee. Recyclability of the developed catalysts and synthetic utility of the prepared Michael adducts for asymmetric synthesis of potential chiral medications via acylation reactions were demonstrated.

Dual-targeted anti-TB/anti-HIV heterodimers.

HIV and M. tuberculosis are two intersecting epidemics making the search for new dual action drugs against both pathogens extremely important. Here, we report on the synthesis and suppressive activities of five dual-targeted HIV/TB compounds.

Evaluation of the antiprotozoan properties of 5'-norcarbocyclic pyrimidine nucleosides.

Carbocyclic nucleoside analogues have a distinguished history as anti-infectious agents, including key antiviral agents. Toxicity was initially a concern but this was reduced by the introduction of 5'-nor variants. Here, we report the result of our preliminary screening of a series of 5'-norcarbocyclic uridine analogues against protozoan parasites, specifically the major pathogens Leishmania mexicana and Trypanosoma brucei.

5-Arylaminouracil Derivatives: New Inhibitors of Mycobacterium tuberculosis.

Three series of 5-arylaminouracil derivatives, including 5-(phenylamino)uracils, 1-(4'-hydroxy-2'-cyclopenten-1'-yl)-5-(phenylamino)uracils, and 1,3-di-(4'-hydroxy-2'-cyclopenten-1'-yl)-5-(phenylamino)uracils, were synthesized and screened for potential antimicrobial activity. Most of compounds had a negative effect on the growth of the Mycobacterium tuberculosis H37Rv strain, with 100% inhibition observed at concentrations between 5 and 40 μg/mL. Of those, 1-(4'-hydroxy-2'-cyclopenten-1'-yl)-3-(4‴-hydroxy-2‴-cyclopenten-1‴-yl)-5-(4″-butyloxyphenylamino)uracil proved to be the most active among tested compounds against the M.

Elongation complexes of Thermus thermophilus RNA polymerase that possess distinct translocation conformations.

We have characterized elongation complexes (ECs) of RNA polymerase from the extremely thermophilic bacterium, Thermus thermophilus. We found that complexes assembled on nucleic acid scaffolds are transcriptionally competent at high temperature (50-80 degrees C) and, depending upon the organization of the scaffold, possess distinct translocation conformations. ECs assembled on scaffolds with a 9 bp RNA:DNA hybrid are highly stable, resistant to pyrophosphorolysis, and are in the posttranslocated state.