Regioselective reactions for programmable resveratrol oligomer synthesis

Although much attention has been devoted to resveratrol, a unique polyphenol produced by plants and credited as potentially being responsible for the 'French paradox'--the observation that French people have a relatively low incidence of coronary heart disease, even though their diet is high in saturated fats--the oligomers of resveratrol have been largely ignored despite their high biological activity. Challenges in achieving their isolation in sufficient quantity from natural sources, coupled with an inability to prepare them easily synthetically, are seen as the main obstacles. Here we report a programmable, controlled and potentially scalable synthesis of the resveratrol family via a three-stage design. The synthetic approach requires strategy- and reagent-guided chemical functionalizations to differentiate two distinct cores possessing multiple sites with the same or similar reactivity, ultimately leading to five higher-order natural products. This work demonstrates that challenging, positionally selective functionalizations of complex materials are possible where biosynthetic studies have indicated otherwise, it provides materials and tools with which to unlock the full biochemical potential of this family of natural products, and it affords an intellectual framework within which other oligomeric families could potentially be accessed.     

Translocation of lipid-linked oligosaccharides across the ER membrane requires Rft1 protein.

N-linked glycosylation of proteins in eukaryotic cells follows a highly conserved pathway. The tetradecasaccharide substrate (Glc3Man9GlcNAc2) is first assembled at the membrane of the endoplasmic reticulum (ER) as a dolichylpyrophosphate (Dol-PP)-linked intermediate, and then transferred to nascent polypeptide chains in the lumen of the ER. The assembly of the oligosaccharide starts on the cytoplasmic side of the ER membrane with the synthesis of a Man5GlcNAc2-PP-Dol intermediate. This lipid-linked intermediate is then translocated across the membrane so that the oligosaccharides face the lumen of the ER, where the biosynthesis of Glc3Man9GlcNAc2-PP-Dol continues to completion. The fully assembled oligosaccharide is transferred to selected asparagine residues of target proteins. The transmembrane movement of lipid-linked Man5GlcNAc2 oligosaccharide is of fundamental importance in this biosynthetic pathway, and similar processes involving phospholipids and glycolipids are essential in all types of cells. The process is predicted to be catalysed by proteins, termed flippases, which to date have remained elusive. Here we provide evidence that yeast RFT1 encodes an evolutionarily conserved protein required for the translocation of Man5GlcNAc2-PP-Dol from the cytoplasmic to the lumenal leaflet of the ER membrane.     

Circles in spermatocyte chromatin loops. Electron microscopy and AgAs-NORs studies

Summary We describe the production of circles in chromomeric loops during the pachytene stage of the spermatocytes. These circles are found attached to chromatin or already free in the nucleoplasm. Each circle measures an average of 3700 Å in circunference. We suggest that such circles might indicate the presence of tandem repetitions.This work was supported by grants from Brazilian National Research Council-CNPq, Fundaçaó de Amparo à Pesquisa do Estado de S. Paulo-FAPESP and Instituto Butantan Research Found-FEDIB.We are grateful to Dr A. Brunner, Jr, for the permission to use the electron microscope.     

Histochemical localization of carbonic anhydrase in Malpighian tubules ofCulex pipiens

Summary Carbonic anhydrase (CA) activity has been localized histochemically by Hansson's method in Malpighian tubules ofCulex pipiens. The enzyme has been observed on membranes of the cytoplasmic inclusions of Malpighian cells; no CA activity has been found in other cytoplasmic structures. The possible meaning of the localization of the enzyme is discussed.     

Oncogenicity of a cell line derived from adenocarcinoma of the salivary gland of C3H/He mouse

Riassunto Cellule portatrici di virus derivate da adenocarcinoma della ghiandola salivare coltivate in vitro sono oncogeniche per l'ospite isogenico per circa sei mesi di coltura. Dopo tale periodo perdono l'oncogenicità e non è più possibile ritrovare particelle virali. Sulla base di questi risultati si conclude che il virus è l'agente causale dell'adenocarcinoma della ghiandola salivare del topo C3H/He.