Synthesis,Characterization, and Biological Evaluation of a Dual-Action Ligand Targeting αvβ3 Integrin and VEGF Receptors

A dual-action ligand targeting both integrin α_Vβ₃ and vascular endothelial growth factor receptors (VEGFRs), was synthesized via conjugation of a cyclic peptidomimetic α_Vβ₃ Arg-Gly-Asp (RGD) ligand with a decapentapeptide. The latter was obtained from a known VEGFR antagonist by acetylation at the Lys13 side chain. Functionalization of the precursor ligands was carried out in solution and in the solid phase, affording two fragments: an alkyne VEGFR ligand and the azide integrin α_Vβ₃ ligand, which were conjugated by click chemistry. Circular dichroism studies confirmed that both the RGD and VEGFR ligand portions of the dual-action compound substantially adopt the biologically active conformation. In vitro binding assays on isolated integrin α_Vβ₃ and VEGFR-1 showed that the dual-action conjugate retains a good level of affinity for both its target receptors, although with one order of magnitude (10/20 times) decrease in potency. The dual-action ligand strongly inhibited the VEGF-induced morphogenesis in Human Umbilical Vein Endothelial Cells (HUVECs). Remarkably, its efficiency in preventing the formation of new blood vessels was similar to that of the original individual ligands, despite the worse affinity towards integrin α_Vβ₃ and VEGFR-1.     

Antiviral Activity of Synthetic Aminopyrrolic Carbohydrate Binding Agents: Targeting the Glycans of Viral gp120 to Inhibit HIV Entry

The binding abilities of a set of structurally related aminopyrrolic synthetic receptors for mannosides, endowed with antimycotic activity against yeast and yeast‐like pathogens bearing mannoproteins on their cell surface, have been investigated towards the highly mannosylated gp120 and gp41 glycoproteins of the HIV envelope. A pronounced binding interaction with both glycoproteins was observed by SPR for most of the investigated compounds. Comparison of their binding properties towards the glycoproteins with their binding affinities toward mannosides revealed a direct correlation, supporting their role as carbohydrate binding agents (CBAs). Cytostatic activity studies revealed antiproliferative activity dependent on the nature and the structure of compounds. Antiviral activity studies against a broad panel of DNA and RNA viruses showed inhibitory effect against HIV infection of the T‐lymphocyte CEM cell line for two compounds, suggesting antiviral activity similar to other CBAs, such as the nonpeptidic pradimicin antibiotics.     

Catalytic Asymmetric Reactions of 4‐Substituted Indoles with Nitroethene: A Direct Entry to Ergot Alkaloid Structures

A domino Friedel–Crafts/nitro‐Michael reaction between 4‐substituted indoles and nitroethene is presented. The reaction is catalyzed by BINOL‐derived phosphoric acid catalysts, and delivers the corresponding 3,4‐ring‐fused indoles with very good results in terms of yields and diastereo‐ and enantioselectivities. The tricyclic benzo[cd]indole products bear a nitro group at the right position to serve as precursors of ergot alkaloids, as demonstrated by the formal synthesis of 6,7‐secoagroclavine from one of the adducts. DFT calculations suggest that the outcome of the reaction stems from the preferential evolution of a key nitronic acid intermediate through a nucleophilic addition pathway, rather than to the expected “quenching” through protonation.     

Computing equilibria of Cournot oligopoly models with mixed-integer quantities

We consider Cournot oligopoly models in which some variables represent indivisible quantities. These models can be addressed by computing equilibria of Nash equilibrium problems in which the players solve mixed-integer nonlinear problems. In the literature there are no methods to compute equilibria of this type of Nash games. We propose a Jacobi-type method for computing solutions of Nash equilibrium problems with mixed-integer variables. This algorithm is a generalization of a recently proposed method for the solution of discrete so-called “2-groups partitionable” Nash equilibrium problems. We prove that our algorithm converges in a finite number of iterations to approximate equilibria under reasonable conditions. Moreover, we give conditions for the existence of approximate equilibria. Finally, we give numerical results to show the effectiveness of the proposed method.     

Brazilian <Emphasis Type="Italic">Dioscoreaceas</Emphasis> starches

Determination of the characteristics of native starches is crucial in order to select their best application in various industrial fields. Thus, two different types of non-traditional native starches from the Dioscoreaceas species (Dioscorea sp. and Dioscorea piperifolia Humb. var. Wild) were studied regarding their thermal, structural and rheological properties. The results were contrasted with traditional commercial starch sources (potato, cassava and corn). From the thermogravimetric results (TG/DTG), D. piperifolia starch obtained the highest thermal stability of the samples, except for potato starch. Furthermore, using differential scanning calorimetry and viscoamylograph profiles (RVA), it was found that the Dioscoreaceas starches presented a higher onset (T _o) temperature and susceptibility to retrogradation. They also showed lower values in relation to relative crystallinity, which was calculated from their X-ray patterns and tendency to white (L*) colour. The shapes of the Discoreaceas starch granules were determined using electron microscopy; it was found that as the potato starch the Dioscoreaceas starches showed a wide range of particle size.     

States on systems of sets that are closed under symmetric difference

We consider extensions of certain states. The states are defined on the systems of sets that are closed under the formation of the symmetric difference (concrete quantum logics). These systems can be viewed as certain set‐representable quantum logics enriched with the symmetric difference. We first show how the compactness argument allows us to extend states on Boolean algebras over such systems of sets. We then observe that the extensions are sometimes possible even for non‐Boolean situations. On the other hand, a difference‐closed system can be constructed such that even two‐valued states do not allow for extensions. Finally, we consider these questions in a σ‐complete setup and find a large class of such systems with rather interesting state properties.     

Sun protection Provided by Regulation School Uniforms in Australian Schools: An Opportunity to Improve Personal Sun protection During Childhood

Childhood sun exposure is linked to excessive pigmented mole development and melanoma risk. Clothing provides a physical barrier, protecting skin from ultraviolet radiation (UVR). Extending sleeves to elbow length and shorts to knee length has been shown to significantly reduce mole acquisition in preschoolers from tropical Queensland. We used publicly available uniform images and guidelines from primary schools in Townsville (latitude 19.25°S, n = 43 schools), Cairns (16.87°S, n = 46) and the Atherton Tablelands (17.26°S, n = 23) in tropical Australia to objectively determine the body surface proportion covered by regulation school uniforms. Uniforms of nongovernment, large (≥800 students), urban, educationally advantaged schools with comprehensive sun protection policies covered more skin than those of government schools (63.2% vs 62.0%; P < 0.001), smaller schools (63.4% vs 62.3%; P = 0.009), rural (62.7% vs 61.9%; P = 0.002) and educationally disadvantaged schools (62.8% vs 62.3%; P < 0.001) with underdeveloped sun protection policies (62.8% vs 62.2%; P = 0.002). Overall, SunSmart and non‐SunSmart school uniforms covered identical body surface proportions (62.4%, P = 0.084). Although wearing regulation school uniforms is mandatory at most Australian primary schools, this opportunity to improve children's sun protection is largely overlooked. Recent evidence suggests that even encouraging minor alterations to school uniforms (e.g. slightly longer sleeves/dresses/skirts/shorts) to increase skin coverage may reduce mole acquisition and melanoma risk, especially in high‐risk populations.     

Mechanism insights into an unexpected isomerisation reaction observed during conversion of N-benzyl piperazinones to corresponding N-benzyl thio-piperazinones

An interesting and surprising rearrangement was observed during the reaction of 4-N-benzyl piperazinone derivatives with Lawesson’s reagent as a thionating agent. Investigation into the possible mechanism responsible for these results is reported herein.     

The molecular level modification of surfaces: from self-assembled monolayers to complex molecular assemblies

The modification of surfaces with self-assembled monolayers (SAMs) containing multiple different molecules, or containing molecules with multiple different functional components, or both, has become increasingly popular over the last two decades. This explosion of interest is primarily related to the ability to control the modification of interfaces with something approaching molecular level control and to the ability to characterise the molecular constructs by which the surface is modified. Over this time the level of sophistication of molecular constructs, and the level of knowledge related to how to fabricate molecular constructs on surfaces have advanced enormously. This critical review aims to guide researchers interested in modifying surfaces with a high degree of control to the use of organic layers. Highlighted are some of the issues to consider when working with SAMs, as well as some of the lessons learnt (169 references).