Purification of hyaluronidase as an anticancer agent inhibiting CD44

Hyaluronidase (Hyal) can be employed to accomplish a diversity of complications related to hyaluronic acid (HA). Hyal contains some classes of catalysts that cleave HA. This enzyme is detected in several human tissues as well as in animal venoms, pathogenic organisms and cancers. Destructive cancer cells regularly increase the CD44 receptor existing in a cell membrane. This receptor acts as an exact receptor for HA, and HA is recognized to motivate the migration, spread, attack and metastasis of cancer cells. Nearly all of the methods used to purify Hyal are highly costly and not proper for industrial applications. This survey aims to review different methods of Hyal purification, which acts as an anticancer agent by degrading HA in tissues and thus inhibiting the CD44–HA interaction. Hyal can be successfully employed in the management of cancer, which is associated with HA–CD44. This review has described different methods for Hyal purification to prepare an origin to develop a novel purification technique for this highly appreciated protein. Using multiple columns is not applicable for the purification of Hyal and thus cannot be used at the industrial level. It is better to use affinity chromatography of anti-Hyal for Hyal with one-step purification.     

Theoretical investigation of the interaction between the metal phthalocyanine [MPc]a(M = Sc,Ti, and V; a = –1, 0, and +1) complexes and formaldehyde

Formaldehyde (FA, CH₂O) is one of the toxic volatile organic compounds that cause harmful effects on the human body. In this work, the interaction of FA gas with metal phthalocyanine (MPc) molecules was studied by employing density functional theory calculations. A variety of [MPc]^a (M = Sc, Ti, and V; a = –1, 0, and +1) complexes were studied, and the electronic properties, interaction energies, and charge transfer properties of all of the studied molecules were systematically discussed. Among the studied complexes, the Sc and Ti phthalocyanines were more reactive toward the adsorption of FA gas. Moreover, it was revealed that the interaction of the [ScPc]⁺¹ and [TiPc]⁰ complexes with the CH₂O molecule was stronger, in which the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) energy gap of 46% and 36% decreased after FA adsorption. The results indicated that the MPc-based materials may be a promising candidate for the detection of FA gas.     

Organocatalytic Strategies for the Development of the Enantioselective Inverse-electron-demand Hetero-Diels-Alder Reaction

Cycloaddition reactions, in particular Diels-Alder reactions, have attracted a lot of attention from organic chemists since they represent one of the most powerful methodologies for the construction of carbon-carbon bonds. In particular, inverse-electron-demand hetero-Diels-Alder reactions have been an important breakthrough for the synthesis of heterocyclic compounds. Among all their variants, the organocatalytic enantioselective version has been widely explored since the asymmetric construction of diversely functionalized scaffolds under reaction conditions encompassed within the green chemistry field is of great interest. In this review, a profound revision on the latest advances on the organocatalytic asymmetric inverse-electron demand hetero-Diels-Alder reaction is shown.     

Surviving Mass Extinctions through Biomineralized DNA

Even in the worst of conditions, such as those which occurred during mass extinction events, life on Earth never totally stopped. Aggressive chemical and physical attacks able to sterilize or poison living organisms occurred repeatedly. Surprisingly, DNA was not degraded, denatured or modified to the point of losing the capability of transferring the genetic information to the next generations. After the events of mass extinction life was able to survive and thrive. DNA was passed on despite being an extremely fragile biomolecule. The potential implications of hydroxyapatite protection of DNA are discussed in this Concept article including how DNA acts as a template for hydroxyapatite (HAp) formation, how cell death can trigger biomineralization, and how DNA can be successfully released from HAp when the conditions are favorable for life.     

Expanding the Scope of Arylsulfonylacetylenes as Alkynylating Reagents and Mechanistic Insights in the Formation of Csp2?Csp and Csp3?Csp Bonds from Organolithiums

We describe the unexpected behavior of the arylsulfonylacetylenes, which suffer an “anti‐Michael” addition of organolithiums producing their alkynylation under very mild conditions. The broad scope, excellent yields, and simplicity of the experimental procedure are the main features of this methodology. A rational explanation of all these results can be achieved by theoretical calculations, which suggest that the association of the organolithiums to the electrophile is a previous step of their intramolecular attack and is responsible for the unexpected “anti‐Michael” reactions observed for substituted sulfonylacetylenes.     

An Efficient,One-Pot Synthesis of Dialkyl 5-Hydroxy-4-aryl-2,5-dihydrofuran-2,3-dicarboxylate Derivatives

The reaction between arylglyoxalmonohydrates, dialkyl acetylenedicarboxylates, and triphenylphosphine is described as a simple and efficient method for the synthesis of 5-hydroxy-4-aryl-2,5-dihydrofuran-2,3-dicarboxylate derivatives.     

Identification of Compounds that Selectively Stabilize Specific G‐Quadruplex Structures by Using a Thioflavin T‐Displacement Assay as a Tool

Small molecules are used in the G‐quadruplex (G4) research field in vivo and in vitro, and there are increasing demands for ligands that selectively stabilize different G4 structures. Thioflavin T (ThT) emits an enhanced fluorescence signal when binding to G4 structures. Herein, we show that ThT can be competitively displaced by the binding of small molecules to G4 structures and develop a ThT‐displacement high‐throughput screening assay to find novel and selective G4‐binding compounds. We screened approximately 28 000 compounds by using three different G4 structures and identified eight novel G4 binders. Analysis of the structural conformation and stability of the G4 structures in presence of these compounds demonstrated that the four compounds enhance the thermal stabilization of the structures without affecting their structural conformation. In addition, all four compounds also increased the G4‐structure block of DNA synthesis by Taq DNA polymerase. Also, two of these compounds showed selectivity between certain Schizosaccharomyces pombe G4 structures, thus suggesting that these compounds or their analogues can be used as selective tools for G4 DNA studies.     

Dissolving Hydroxyolite: A DNA Molecule into Its Hydroxyapatite Mold

In spite of the clinical importance of hydroxyapatite (HAp), the mechanism that controls its dissolution in acidic environments remains unclear. Knowledge of such a process is highly desirable to provide better understanding of different pathologies, as for example osteoporosis, and of the HAp potential as vehicle for gene delivery to replace damaged DNA. In this work, the mechanism of dissolution in acid conditions of HAp nanoparticles encapsulating double‐stranded DNA has been investigated at the atomistic level using computer simulations. For this purpose, four consecutive (multi‐step) molecular dynamics simulations, involving different temperatures and proton transfer processes, have been carried out. Results are consistent with a polynuclear decalcification mechanism in which proton transfer processes, from the surface to the internal regions of the particle, play a crucial role. In addition, the DNA remains protected by the mineral mold and transferred proton from both temperature and chemicals. These results, which indicate that biomineralization imparts very effective protection to DNA, also have important implications in other biomedical fields, as for example in the design of artificial bones or in the fight against osteoporosis by promoting the fixation of Ca²⁺ ions.     

Rotaxane‐Like Structures Threaded through the Pores of Hollow Porous Nanocapusles

Nanocapsules with molecules threaded through the porous shells may lead to advanced cell‐mimicking functional devices. Herein, we show the feasibility of synthesizing such hybrid nanostructures by using vesicle‐templated polymer nanocapsules with controlled nanopores. Ship‐in‐a‐bottle assembly inside a nanocapsule created an internal unit. An external unit was then connected to an entrapped internal unit through pre‐attached linker threaded through a nanopore in the shell of the nanocapsule. Both internal and external units are larger than the pore size and cannot cross the shell, producing a rotaxane‐like structure. Successful synthesis was achieved with fairly short linkers (six and ten carbon atoms in a chain), creating an opportunity for facile synthesis of functional devices capable of cross‐shell communication.