Design and evaluation of consensus PCR assays for henipaviruses.

Henipaviruses were first discovered in the 1990s, and their potential threat to public health is of increasing concern with increasing knowledge. Old-world fruit bats are the reservoir hosts for these viruses, and spill-over events cause lethal infections in a wide range of mammalian species, including humans. In anticipation of these spill-over events, and to investigate further the geographical range of these genetically diverse viruses, assays for detection of known and potentially novel strains of henipaviruses are required. The development of multiple consensus PCR assays for the detection of henipaviruses, including both SYBR Green and TaqMan real-time PCRs and a conventional heminested PCR is described. The assays are highly sensitive and have defined specificity. In addition to being useful tools for detection of known and novel henipaviruses, evaluation of assay efficiency and sensitivity across both biological and synthetic templates has provided valuable insight into consensus PCR design and use.

In vitro and In vivo inhibition of LPS-stimulated tumor necrosis factor-alpha secretion by the gallotannin beta-D-pentagalloylglucose.

The naturally occurring gallotannin beta-D-pentagalloylglucose (beta-PGG) decreases tumor necrosis factor-alpha (TNF-alpha) output from human peripheral blood mononucleocytes exposed to lipopolysaccharide (LPS) by as much as 90% (vs control) at approximately 5 microM concentration. A qualitatively similar but less pronounced effect ( approximately 50% decrease) was observed in the serum of rats dosed with both LPS and beta-PGG. These results may have relevance to therapies that target disease states characterized by an overproduction of TNF-alpha.

Alkynyliodonium salts in organic synthesis. Dihydrofuran formation via a formal stevens shift of a carbon substituent within a disubstituted-carbon oxonium ylide.

The addition of p-toluenesulfinate to the silyl, 1-furanyl, and 1-pyranyl ethers of 1-hydroxybut-3-ynyl(phenyl)iodonium triflate triggers a sequence of reactions that ultimately delivers 2-substituted 3-p-toluenesulfonyldihydrofuran products in variable yields. A putative 1,2-group shift within an unsaturated oxonium ylide (Stevens rearrangement) accounts for the oxygen-to-carbon transfer of the ether substituent. Deuterium labeling studies clarify the mechanistic course of this shift by providing evidence consistent with intramolecular substituent transfer and by identifying the primary source of the proton that intercepts the ylide in the major yield-limiting process.

Ellagitannin chemistry. Evolution of a three-component coupling strategy for the synthesis of the dimeric ellagitannin coriariin A and a dimeric gallotannin analogue.

The total synthesis of the dimeric ellagitannin coriariin A is reported. The key reaction to access the dimeric framework was realized early in the synthesis pathway via a bis acylation reaction of a dehydrodigalloyl diacid with 2 equiv of a glucopyranose trichloroacetimidate. The glucose rings were subsequently functionalized, culminating in a double oxidative cyclization to form stereoselectively both (S)-HHDP ester units. This bis acylation strategy was also employed to prepare a gallotannin analogue of coriariin A whose earlier synthesis by orthoquinone dimerization was plagued by yield-limiting side reactions.

Alkynyliodonium salts in organic synthesis. Preparation of 2-substituted-3-p-toluenesulfonyldihydrofurans from 1-hydroxybut-3-ynyliodonium ethers via a formal Stevens shift of a carbon group.

[reaction: see text]p-Toluenesulfinate addition to 1-hydroxybut-3-ynyliodonium ethers triggers a sequence of reactions which ultimately delivers 2-substituted-3-p-toluenesulfonyldihydrofuran products along with 3-p-toluenesulfonyldihydrofuran as a major byproduct. A putative 1,2-alkyl shift within an unsaturated oxonium ylide (Stevens rearrangement) accounts for the oxygen-to-carbon transfer of the alkyl group.

Binding affinities of gallotannin analogs with bovine serum albumin: ramifications for polyphenol-protein molecular recognition.

A series of gallotannin analogs were prepared by chemical synthesis, and their affinity for the test-case protein bovine serum albumin was measured by equilibrium dialysis. The structure/activity data obtained suggest that the naturally occurring gallotannins, in fact, do not represent the optimal protein recognition agents amongst polyphenolated templates.

Immunostimulation by plant polyphenols: a relationship between tumor necrosis factor-alpha production and tannin structure.

The ability of the naturally occurring tumoricidal ellagitannin coriariin A to stimulate secretion of both IL-1beta and TNF-alpha from human peripheral blood mononuclear cells has been demonstrated. Companion studies with the monomeric gallotannin beta-D-pentagalloylglucose and a synthesized dimeric gallotannin-ellagitannin hybrid suggest that TNF-alpha rather than IL-1beta is the causative agent in tannin-mediated antitumor action in vivo, in contrast to an ealier proposal.