Synthesis and Antiviral Evaluation of Adenosine-N1-Oxide and 1-(Benzyloxy) Adenosines

Abstract

The antiviral activity of adenosine-N¹-oxide (1) and a variety of substituted 1-(benzyloxy) adenosines (2) has been re-investigated and significant in vitro activity vs. Vaccinia virus has been shown. In vivo activity in mice has also been demonstrated.     

Synthesis of Iodoaminoimidazole Arabinoside (IAIA): A Potential Reductive Metabolite of the Spect Imaging Agent,Iodoazomycin Arabinoside (IAZA)

Abstract

The stereospecific synthesis of 1-(5-deoxy-5-iodo-α-D-arabino-furanosyl)-2-aminoimidazole (iodoaminoimidazole arabinoside: IAIA, 2) is described. The reaction of the protected sugar bromide (8) and trifluoroacetamidoimidazole (10B) gave the coupled product (11B), which gave the free nucleoside (4) on deblocking. It was identical with AIA obtained by reduction of AZA (azomycin arabinoside), whose anomeric configuration was found to be a by the X-ray crystallography.     

Analysis of Modified Deoxynucleosides by Electrospray Ionization Mass SPECTROMETRY

Abstract

Electrospray mass spectra for selected modified deoxynucleosides and deoxynucleoside monophosphates have been determined. Protonated molecular ions are abundant in the positive ion spectrum, while (M-H) appears in the negative ion spectrum. However, fragment ion intensities are usually low in both spectra. Conditions which promote collision-induced dissociation within the electrospray source facilitate fragment ion formation, and the intensity of BH₂ ⁺ and S⁺ (positive ion spectrum) and (M-BH) and B (negative ion spectrum) are enhanced by increasing the skimmer cone voltage. MH⁺ was detected with as little as 3 pmol of deoxynucleoside, and the protonated molecular ion intensity is linear with respect to analyte concentration over two orders of magnitude.     

Two Hydrolase Resistant Analogues of Diadenosine 5′,5″′-P,P-Triphosphate for Studies with FHIT,The Human Fragile Histidine Triad Protein¶

Abstract

The design and synthesis of analogues of diadenosine 5′,5″′-P,P-triphosphate that are resistant to pyrophosphate hydrolysis is described in relation to their rôle in signalling and tumorigenesis involving the Fhit protein, the human fragile histidine triad protein, which is a novel Ap3A binding/cleaving protein.

     

A revision of the continental species of Copa Simon, 1885 (Araneae,Corinnidae) in the Afrotropical Region

The cryptic ground-dwelling castianeirine genus Copa Simon, 1885 (Araneae: Corinnidae) is revised in the continental Afrotropical Region. The type species of the genus, Copa flavoplumosa Simon, 1885, is redescribed and considered a senior synonym of Copa benina Strand, 1916 syn. n. and Copa benina nigra Lessert, 1933 syn. n. It is widespread throughout the Afrotropical Region but has not been introduced to any of the associated regional islands. A new species, Copa kei sp. n., is described from South Africa. Copa agelenina Simon, 1910, originally described from a subadult female from southern Botswana, is considered a nomen dubium. Copa flavoplumosa is a characteristic species of leaf litter spider assemblages and is particularly prevalent in savanna habitats on the continent, but also occurs in various forest types, grasslands, fynbos and semi-arid Nama Karoo habitats. In contrast, Copa kei sp. n. has only been recorded from Afromontane and coastal forests in south-eastern South Africa.     

Potential seed dispersal distances of native and non-native fleshy fruiting shrubs in the South African Mediterranean climate region

Bird flight distances for the small Zosterops capensis, the medium-size Pycnonotus capensis and the large Colius striatus were extracted from these birds’ initial ring and subsequent recapture locations and expressed on equivalent per km bases. The products of the bird-ring recapture records in nine different flight distance categories and daily consumption rates by these birds of seeds of two native (Chrysanthemoides monilifera and Olea europaea spp. africana) and two alien (Lantana camara and Solanum mauritianum) shrubs were used to construct seed dispersal curves. The dispersal distances to which ingested seeds were theoretically restricted were computed from the product of the retention time of seed in the birds’ guts and their flight speeds using published functions. All three bird species displayed thin long-tailed seed dispersal curves characterized by peaks at distances below 1 km which declined progressively with increasing distances, the tails extending to distances of up to 400 km. Flight distances corresponding with predicted seed gut retention times were 9.4 km in the small Z. capensis, 17.8 km in the medium size P. capensis and 21.2 km in the large C. striatus. These potential seed dispersal distances were much greater that the frequently reported long distance seed dispersal threshold of 1 km by frugivorous birds in fragmented landscapes.     

Intestinal caveolin-1 is important for dietary fatty acid absorption

How dietary fatty acids are absorbed into the enterocyte and transported to the ER is not established. We tested the possibility that caveolin-1 containing lipid rafts and endocytic vesicles were involved. Apical brush border membranes took up 15% of albumin bound ³H-oleate whereas brush border membranes from caveolin-1 KO mice took up only 1%. In brush border membranes, the ³H-oleate was in the detergent resistant fraction of an OptiPrep gradient. On OptiPrep gradients of intestinal cytosol, we also found the ³H-oleate in the detergent resistant fraction, separate from OptiPrep gradients spiked with ³H-oleate or ³H-triacylglycerol. Caveolin-1 immuno-depletion of cytosol removed 91% of absorbed ³H-oleate whereas immuno-depletion using IgG, or anti-caveolin-2 or -3 or anti-clathrin antibodies removed 20%. Electron microscopy showed the presence of caveolin-1 containing vesicles in WT mouse cytosol that were 4 fold increased by feeding intestinal sacs 1 mM oleate. No vesicles were seen in caveolin-1 KO mouse cytosol. Caveolin-1 KO mice gained less weight on a 23% fat diet and had increased fat in their stool compared to WT mice. We conclude that dietary fatty acids are absorbed by caveolae in enterocyte brush border membranes, are endocytosed, and transported in cytosol in caveolin-1 containing endocytic vesicles.