Regio- and stereoselective syntheses of the natural product CCR5 antagonist anibamine and its three olefin isomers

The syntheses of the natural product anibamine and its three olefin isomers have been achieved concisely and efficiently via highly regio- and stereoselective reactions. The crucial steps included a regioselective palladium-catalyzed alkynylation by Sonogashira coupling and a stereoselective Suzuki coupling. Further conformation analyses and in vitro calcium mobilization studies were carried out to characterize the compounds' biological properties.     

Both systemic and local application of Granulocyte-colony stimulating factor (G-CSF) is neuroprotective after retinal ganglion cell axotomy

Background  

The hematopoietic Granulocyte-Colony Stimulating Factor (G-CSF) plays a crucial role in controlling the number of neutrophil progenitor cells. Its function is mediated via the G-CSF receptor, which was recently found to be expressed also in the central nervous system. In addition, G-CSF provided neuroprotection in models of neuronal cell death. Here we used the retinal ganglion cell (RGC) axotomy model to compare effects of local and systemic application of neuroprotective molecules.     

Analysis of protein denaturation by high-performance continuous differential viscometry

The intrinsic viscosity of protein solutions changes when denaturation occurs. Therefore, viscosity measurement using traditional glass capillary viscometers has been a key method to study the process of protein denaturation. Such measurements are laborious, time consuming and need at least 10 ml of sample. The Viscotek differential viscometer can be used as an on-line detector for high-performance liquid chromatography to monitor the viscosity of column effluent. In this study, samples were injected using an autosampler onto a "delay" column containing glass beads in place of the high-performance liquid chromatography columns. Results indicate guanidine hydrochloride, heat and pH act as denaturing agents and changes the intrinsic viscosities of serum albumin, turkey egg albumin, and ovalbumin solutions. The differential viscometer is sensitive and provides accurate measurements of minor changes in viscosities of very dilute protein solutions undergoing denaturation. The advantage of using the differential viscometer instead of conventional glass capillary viscometer is the increased sensitivity, precision, speed and operational ease that permits measurements of solution viscosity of low sample concentrations up to 1.2 micrograms of pure proteins.     

Round trip radical reactions from acyclic precursors to tricyclo [5.3.1.0]undecanes. A new cascade radical cyclization approach to (+/-)-isogymnomitrene and (+/-)-gymnomitrene

The synthesis and "round trip radical cyclization" of 11-iodo-2,7,11-trimethyldodec-6-en-5-one are described. The round trip cyclization is a sequence of 5-exo, 6-endo, and 5-exo cyclizations in which the last radical cyclization occurs at the same carbon atom as the initial radical generation. The key second (6-endo) cyclization produces two stereoisomers, one of which cyclizes efficiently to isogymnomitrene ketone, while the other cyclizes inefficiently to gymnomitrene ketone. Efforts to influence the kinetic or thermodynamic outcome of the second cyclization were not successful, and the results are contrasted with a related cyclization of Jung and Rayle where thermodynamic control was readily established.     

Poly(2-oxazoline)-Based Polyplexes as a PEG-Free Plasmid DNA Delivery Platform

The present study expands the versatility of cationic poly(2-oxazoline) (POx) copolymers as a polyethylene glycol (PEG)-free platform for gene delivery to immune cells, such as monocytes and macrophages. Several block copolymers are developed by varying nonionic hydrophilic blocks (poly(2-methyl-2-oxazoline) (pMeOx) or poly(2-ethyl-2-oxazoline) (pEtOx), cationic blocks, and an optional hydrophobic block (poly(2-isopropyl-2-oxazoline) (iPrOx). The cationic blocks are produced by side chain modification of 2-methoxy-carboxyethyl-2-oxazoline (MestOx) block precursor with diethylenetriamine (DET) or tris(2-aminoethyl)amine (TREN). For the attachment of a targeting ligand, mannose, azide-alkyne cycloaddition click chemistry methods are employed. Of the two cationic side chains, polyplexes made with DET-containing copolymers transfect macrophages significantly better than those made with TREN-based copolymer. Likewise, nontargeted pEtOx-based diblock copolymer is more active in cell transfection than pMeOx-based copolymer. The triblock copolymer with hydrophobic block iPrOx performs poorly compared to the diblock copolymer which lacks this additional block. Surprisingly, attachment of a mannose ligand to either copolymer is inhibitory for transfection. Despite similarities in size and design, mannosylated polyplexes result in lower cell internalization compared to nonmannosylated polyplexes. Thus, PEG-free, nontargeted DET-, and pEtOx-based diblock copolymer outperforms other studied structures in the transfection of macrophages and displays transfection levels comparable to GeneJuice, a commercial nonlipid transfection reagent.     

Reduction of α,β-unsaturated nitroolefins into nitroalkanes with Hantzsch ester promoted by isothiouronium salts

α,β-Unsaturated nitroolefins were reduced into nitroalkanes with a Hantzsch ester, promoted by S-benzyl isothiouronium iodide. The reactions proceeded successfully to afford the desired products in high yields and with excellent chemoselectivity.     

An adeno-associated viral vector transduces the rat hypothalamus and amygdala more efficient than a lentiviral vector

Background  

This study compared the transduction efficiencies of an adeno-associated viral (AAV) vector, which was pseudotyped with an AAV1 capsid and encoded the green fluorescent protein (GFP), with a lentiviral (LV) vector, which was pseudotyped with a VSV-G envelop and encoded the discosoma red fluorescent protein (dsRed), to investigate which viral vector transduced the lateral hypothalamus or the amygdala more efficiently. The LV-dsRed and AAV1-GFP vector were mixed and injected into the lateral hypothalamus or into the amygdala of adult rats. The titers that were injected were 1 × 10⁸ or 1 × 10⁹ genomic copies of AAV1-GFP and 1 × 10⁵ transducing units of LV-dsRed.     

Picomolar antimalarial agent from a Chinese medicinal plant

In our long-term efforts searching for antimalarial agents from Chinese medicinal plants,seven novel dimeric sesquiterpenoids(1–7)with significant antimalarial activity were isolated and characterized from the whole plants of Sarcandra glabra subsp.brachystachys by solid data acquired by diverse methods.Among them,compound 3 with an EC50 value of 4.3 pM against the chloroquine-resistant Plasmodium falciparum is the most potent antimalarial agent reported hitherto,about 1,000-fold stronger than artemisinin.This article further consolidates and refines our previously delineated structure-activity relationship for this antimalarial compound class.