Human cytomegalovirus (HCMV) is a widespread pathogen that can cause severe disease in immunologically immature and immunocompromised individuals. Cyclopropavir (CPV) is a guanine nucleoside analog active against human and murine cytomegaloviruses in cell culture and efficacious in mice by oral administration. Previous studies established that the mechanism of action of CPV involves inhibition ...

We describe a convergent, enantioselective synthesis of (-)-tetracycline (1) from benzoic acid (17 steps, 1.1% yield). Benzoic acid was transformed into the AB precursor 2 in 10 steps (11% yield), as previously described, and the latter compound was activated toward Diels-Alder cycloaddition by the introduction of an alpha-phenylthio group (two steps, 66% yield). Heating of the resulting alpha-...

Abstract Background Halogenation is a recurring feature in natural products, especially those from marine organisms. The selectivity with which halogenating enzymes act on their substrates renders halogenases interesting targets for biocatalyst development. Recently, CylC – the first predicted dimetal-carboxylate halogenase to be characterized was shown regio- and stereoselectively install chlo...

The palladium-catalyzed cross-coupling reaction between organoboron compounds and organic halides or triflates provides a powerful and general methodology for the formation of carbon–carbon bonds. Recently, this reaction has been called the Suzuki coupling, Suzuki reaction, or Suzuki–Miyaura coupling, although we never referred to it as such previously. In this review, this name will be used wi...

The appearance of P-adrenergic receptors and isoproterenol-stimulated adenylate cyclase during differentiation of embryonic quail muscle cells in tissue culture has been examined. P-Adrenergic receptors first appear during the fusion stage of myogenesis. ['"I]]Iodohydroxybenzylpindolol (['2sI]IHYP) was used as the ligand to characterize &adrenergic receptors. In equilibrium binding studies, mat...

A series of 2-, 3- and 4-substituted pyridines was metabolised using the mutant soil bacterium Pseudomonas putida UV4 which contains a toluene dioxygenase (TDO) enzyme. The regioselectivity of the biotransformation in each case was determined by the position of the substituent. 4-Alkylpyridines were hydroxylated exclusively on the ring to give the corresponding 4-substituted 3-hydroxypyridines,...

To determine the level of FMO1 protein present in human liver tissues, a monospecific antibody was prepared and a sensitive Western blotting procedure with enhanced chemiluminescence detection was developed. Human FMO1, purified from insect cells expressing the recombinant protein, was used as a protein standard for absolute quantification. The average concentrations of FMO1 in microsomes prepa...

A novel dioxygenase from Burkholderia ambifaria AMMD (SadA) stereoselectively catalyzes the C3-hydroxylation of N-substituted branched-chain or aromatic L-amino acids, especially N-succinyl-L-leucine, coupled with the conversion of α-ketoglutarate to succinate and CO2. To elucidate the structural basis of the substrate specificity and stereoselective hydroxylation, we determined the crystal str...

We recently isolated a cDNA clone for the human cholecystokinin (CCK)B/gastrin receptor and permanently expressed this receptor cDNA in NIH-3T3 cells. [125I]CCK-8 specifically bound to the membrane of the transfectant, and this binding was displaced by unlabeled CCK-8 with an IC50 of 0.32 nM. Treatment of these cells with CCK-8 increased the intracellular Ca2+ concentration with an EC50 of 0.30...

Monoand bis(q-cyclopentadieny1)zirconium complexes show interesting stereochemical features with regard to their use in organometallic and organic synthesis as well as in catalysis. An example is described where the zirconocene unit serves to stabilize a planar tetracoordinate carbon center. Next, various building blocks (a metal carbonyl, an organic carbonyl compound, a conjugated diene, plus ...