Versatile Scaffold Research Articles

Incorporation of fibrin into a collagen–glycosaminoglycan matrix results in a scaffold with improved mechanical properties and enhanced capacity to resist cell-mediated contraction

Fibrin has many uses as a tissue engineering scaffold, however many in vivo studies have shown a reduction in function resulting from the susceptibility of fibrin to cell-mediated contraction. The overall aim of the present study was to develop and characterise a reinforced natural scaffold using fibrin, collagen and glycosaminoglycan (FCG), and to examine the cell-mediated contraction of this scaffold in comparison to fibrin gels. Through the use of an injection loading technique, a homogenous FCG scaffold was developed. Mechanical testing showed a sixfold increase in compressive modulus and a thirtyfold increase in tensile modulus of fibrin when reinforced with a collagen–glycosaminoglycan backbone structure. Human vascular smooth muscle cells (vSMCs) were successfully incorporated into the FCG scaffold and demonstrated excellent viability over 7days, while proliferation of these cells also increased significantly. VSMCs were seeded into both FCG and fibrin-only gels at the same seeding density for 7days and while FCG scaffolds did not demonstrate a reduction in size, fibrin-only gels contracted to 10% of their original diameter. The FCG scaffold, which is composed of natural biomaterials, shows potential for use in applications where dimensional stability is crucial to the functionality of the tissue. Statement of SignificanceFibrin is a versatile scaffold for tissue engineering applications, but its weak mechanical properties leave it susceptible to cell-mediated contraction, meaning the dimensions of the fibrin construct will change over time. We have reinforced fibrin with a collagen glycosaminoglycan matrix and characterised the mechanical properties and bioactivity of the reinforced fibrin (FCG). This is the first scaffold manufactured from all naturally derived materials that resists cell-mediated contraction. In fact, over 7days, the FCG scaffold fully resisted cell-mediated contraction of vascular smooth muscle cells. This FCG scaffold has many potential applications where natural scaffold materials can encourage regeneration.

Aggregation-Induced Förster Resonance Energy Transfer in Polybenzofulvene/Dye Nanoparticles

Polymeric nanoparticles are versatile scaffolds to develop smart multichromophoric systems whose collective optical properties can be tuned in view of a specific application. Addition of water (nonsolvent) to diluted THF solutions of a blue emitting π-stacked polymer and a yellow emitting dye induces nanoparticle polymer/dye coaggregation. At 70% water content, concomitantly to nanoparticle shrinking, the emission efficiency increases and the color switches from blue to yellow. Time-resolved fluorescence analysis demonstrates that the switch in the nanoparticle emission is governed by an aggregation-induced Forster resonance energy transfer (FRET) process from the polymer to the molecularly embedded dye activated at a local concentration of about 10–2 M within the nanoparticles.

Cascade DNA nanomachine and exponential amplification biosensing.

DNA is a versatile scaffold for the assembly of multifunctional nanostructures, and potential applications of various DNA nanodevices have been recently demonstrated for disease diagnosis and treatment. In the current study, a powerful cascade DNA nanomachine was developed that can execute the exponential amplification of p53 tumor suppressor gene. During the operation of the newly-proposed DNA nanomachine, dual-cyclical nucleic acid strand-displacement polymerization (dual-CNDP) was ingeniously introduced, where the target trigger is repeatedly used as the fuel molecule and the nicked fragments are dramatically accumulated. Moreover, each displaced nicked fragment is able to activate the another type of cyclical strand-displacement amplification, increasing exponentially the value of fluorescence intensity. Essentially, one target binding event can induce considerable number of subsequent reactions, and the nanodevice was called cascade DNA nanomachine. It can implement several functions, including recognition element, signaling probe, polymerization primer and template. Using the developed autonomous operation of DNA nanomachine, the p53 gene can be quantified in the wide concentration range from 0.05 to 150 nM with the detection limit of 50 pM. If taking into account the final volume of mixture, the detection limit is calculated as lower as 6.2 pM, achieving an desirable assay ability. More strikingly, the mutant gene can be easily distinguished from the wild-type one. The proof-of-concept demonstrations reported herein is expected to promote the development and application of DNA nanomachine, showing great potential value in basic biology and medical diagnosis.

ChemInform Abstract: Hydrindacenes as Versatile Supramolecular Scaffolds

AbstractReview: [35 refs.

Design of a Versatile and Improved Precatalyst Scaffold for Palladium-Catalyzed Cross-Coupling: (η3-1-tBu-indenyl)2(μ-Cl)2Pd2

We describe the development of (η3-1-tBu-indenyl)2(μ-Cl)2Pd2, a versatile precatalyst scaffold for Pd-catalyzed cross-coupling. Our new system is more active than commercially available (η3-cinnamyl)2(μ-Cl)2Pd2 and is compatible with a range of NHC and phosphine ligands. Precatalysts of the type (η3-1-tBu-indenyl)Pd(Cl)(L) can either be isolated through the reaction of (η3-1-tBu-indenyl)2(μ-Cl)2Pd2 with the appropriate ligand or generated in situ, which offers advantages for ligand screening. We show that the (η3-1-tBu-indenyl)2(μ-Cl)2Pd2 scaffold generates highly active systems for a number of challenging cross-coupling reactions. The reason for the improved catalytic activity of systems generated from the (η3-1-tBu-indenyl)2(μ-Cl)2Pd2 scaffold compared to (η3-cinnamyl)2(μ-Cl)2Pd2 is that inactive PdI dimers are not formed during catalysis.

Editorial: multidrug resistance in cancer: pharmacological strategies from basic research to clinical issues.

EDITORIAL article Front. Oncol., 11 May 2015Sec. Pharmacology of Anti-Cancer Drugs https://doi.org/10.3389/fonc.2015.00105

Self-assembly of cricoid proteins induced by "soft nanoparticles": an approach to design multienzyme-cooperative antioxidative systems.

A strategy to construct high-ordered protein nanowires by electrostatic assembly of cricoid proteins and "soft nanoparticles" was developed. Poly(amido amine) (PAMAM) dendrimers on high generation that have been shown to be near-globular macromolecules with all of the amino groups distributing throughout the surface were ideal electropositive "soft nanoparticles" to induce electrostatic assembly of electronegative cricoid proteins. Atomic force microscopy and transmission electron microscopy all showed that one "soft nanoparticle" (generation 5 PAMAM, PD5) could electrostatically interact with two cricoid proteins (stable protein one, SP1) in an opposite orientation to form sandwich structure, further leading to self-assembled protein nanowires. The designed nanostructures could act as versatile scaffolds to develop multienzyme-cooperative antioxidative systems. By means of inducing catalytic selenocysteine and manganese porphyrin to SP1 and PD5, respectively, we successfully designed antioxidative protein nanowires with both excellent glutathione peroxidase and superoxide dismutase activities. Also, the introduction of selenocysteine and manganese porphyrin did not affect the assembly morphologies. Moreover, this multienzyme-cooperative antioxidative system exhibited excellent biological effect and low cell cytotoxicity.

The Development of a Versatile Trifunctional Scaffold for Biological Applications

AbstractWe describe the synthesis of a trifunctional scaffold constructed from a planar core of trimesic acid derivatized with three propargylamine moieties. The scaffold was attached to a solid‐phase resin through the carboxylic group of a fluorinated alkyl spacer arm. The orthogonal protection of two of the alkyne groups with triethylsilyl and triisopropylsilyl moieties enabled modular and efficient derivatization of the scaffold with three different azides by using solid‐phase synthesis on amphiphilic ChemMatrix resin. We showed that a fluorine label can be used to quantify the content of fluorine‐containing compounds by 19F NMR spectroscopic analysis after cleavage from the resin. We have thus designed a versatile and convenient tool that could be useful for simple and rapid solid‐phase syntheses of combinatorial libraries of the scaffold‐based compounds, for example as new protein binders.

ChemInform Abstract: Recent Advances in Development of Imidazo[1,2‐a]pyrazines: Synthesis, Reactivity and Their Biological Applications

AbstractReview: [96 refs.

Facile one pot synthesis of 8-chloro-[1,2,4]triazolo[4,3-a]pyrazines via oxidative cyclisation using chloramine T

A facile and expedient one pot synthesis of 8-chloro-[1,2,4]triazolo[4,3-a]pyrazine derivatives from 2-chloro-3-hydrazinylpyrazine and aldehydes is described using chloramine T trihydrate as a safe and convenient electrocyclisation (oxidising) agent. The presence of the chloro group on pyrazine enabled us to access versatile new synthetic scaffolds by easy diversification using palladium catalysed Suzuki–Miyaura and Sonogashira cross coupling reactions. The products are obtained in high yields in short reaction time under mild conditions without the need for chromatographic purification.

Hydrindacenes as Versatile Supramolecular Scaffolds

Abstract This report describes the synthesis and structural features of supramolecular assemblies of s-hydrindacene (1,2,3,5,6,7-hexahydro-s-indacene), such as macrocycles with directionally persistent peripheral functionality, allosteric receptors, adrenaline receptors, and rotaxane molecular shuttles. These hydrindacene-based assemblies also exhibit allostericity due to induced polarization of amides or to entropy-driven switching between the imine and hydrogen bonds.

ChemInform Abstract: Isohexides as Versatile Scaffolds for Asymmetric Catalysis

AbstractReview: [46 refs.

M13 Virus-Enabled Synthesis of Titanium Dioxide Nanowires for Tunable Mesoporous Semiconducting Networks

Mesoporous semiconducting networks exhibit advantageous photoelectrochemical properties. The M13 virus is a versatile biological scaffold that has been genetically engineered to organize various materials into nanowire (NW)-based mesoporous structures. In this study, high-aspect ratio titanium dioxide NWs are synthesized by utilizing M13 viruses as templates, and the NWs are assembled into semiconducting mesoporous networks with tunable structural properties. To understand the effects of different morphologies on the photovoltaic performance, the as-fabricated networks are employed as photoanodes in liquid-state dye-sensitized solar cells (DSCs). Compared with traditional nanoparticle-based photoanodes, the NW-based DSC photoanodes demonstrate much higher electron diffusion lengths while maintaining a comparable light harvesting capacity, thus leading to improved power conversion efficiencies. In addition, the NW-based semiconducting mesoporous thin films are able to load sufficient organolead iodide perovskite materials into the interconnected pores, and the perovskite-coated films are utilized as efficient photoanodes for solid-state organolead iodide perovskite hybrid solar cells and achieve power conversion efficiencies superior to those of liquid-state DSCs.

Structural basis for carbohydrate binding properties of a plant chitinase-like agglutinin with conserved catalytic machinery.

A new chitinase-like agglutinin, RobpsCRA, related to family GH18 chitinases, has previously been identified in black locust (Robinia pseudoacacia) bark. The crystal structure of RobpsCRA at 1.85Å resolution reveals unusual molecular determinants responsible for the lack of its ancestral chitinase activity. Unlike other chitinase-like proteins, which lack chitinase catalytic residues, RobpsCRA has conserved its catalytic machinery. However, concerted rearrangements of loop regions coupled to non-conservative substitutions of aromatic residues central to the chitin-binding groove explain the lack of hydrolytic activity against chitin and the switch toward recognition of high-mannose type N-glycans. Identification of close homologs in flowering plants with conservation of sequence motifs associated to the structural adaptations seen in RobpsCRA defines an emerging class of agglutinins, as emphasized by a phylogenetic analysis, that are likely to share a similar carbohydrate binding specificity for high-mannose type N-glycans. This study illustrates the recent evolution and molecular adaptation of a versatile TIM-barrel scaffold within the ancestral GH18 family.

ChemInform Abstract: Recent Advances in the Synthesis of 2‐Substituted Benzothiazoles: A Review

AbstractReview: 184 refs.

ChemInform Abstract: 2,3‐Dihydropyridin‐4(1H)‐ones and 3‐Aminocyclohex‐2‐enones: Synthesis, Functionalization, and Applications to Alkaloid Synthesis

AbstractReview: [51 refs.

Dendrimer-entrapped metal colloids as imaging agents.

This review reports the recent advances in dendrimer-entrapped metal colloids as contrast agents for biomedical imaging applications. The versatile dendrimer scaffolds with 3-dimensional spherical shape, highly branched internal cavity, tunable surface conjugation chemistry, and excellent biocompatibility and nonimmunogenicity afford their uses as templates to create multifunctional dendrimer-entrapped metal colloids for mono- or multi- mode molecular imaging applications. In particular, multifunctional dendrimer-entrapped gold nanoparticles with different surface modifications have been used for fluorescence imaging, targeted tumor computed tomography (CT) imaging, enhanced blood pool CT imaging, dual mode CT/MR imaging, and tumor theranostics (combined CT imaging and chemotherapy) will be introduced and discussed in detail.

Recapitulation of in vivo-like neutrophil transendothelial migration using a microfluidic platform.

Neutrophil transendothelial migration (TEM) is an essential physiological process that regulates the recruitment of neutrophils in response to inflammatory signals. Herein, a versatile hydrogel scaffold is embedded in a microfluidic platform that supports an endothelial cell layer cultured in the vertical direction and highly stable chemical gradients; this construct is employed to mimic the in vivo neutrophil TEM process. We found that the number of neutrophils migrating across the endothelial cell layer is dependent on the presented chemoattractant concentration and the spatial profile of the chemical gradient. Endothelial cells play a critical role in neutrophil TEM by promoting neutrophil morphological changes as well as expressing surface receptor molecules that are indispensable for inducing neutrophil attachment and migration. Furthermore, the microfluidic device also supports competing chemoattractant gradients to facilitate neutrophil TEM studies in complex microenvironments that more accurately model the in vivo system than simplified microenvironments without the complexity of chemical gradients. This work demonstrates that combinations of any two different chemoattractants induce more significant neutrophil migration than a single chemoattractant in the same total amount, indicating synergistic effects between distinct chemoattractants. The in vitro reconstitution of neutrophil TEM successfully translates planar neutrophil movement into in vivo-like neutrophil recruitment and accelerates understanding of cellular interactions between neutrophils and endothelial cells within the complicated physiological milieu.

Ubiquitin is a versatile scaffold protein for the generation of molecules with de novo binding and advantageous drug-like properties

In the search for effective therapeutic strategies, protein-based biologicals are under intense development. While monoclonal antibodies represent the majority of these drugs, other innovative approaches are exploring the use of scaffold proteins for the creation of binding molecules with tailor-made properties. Ubiquitin is especially suited for this strategy due to several key characteristics. Ubiquitin is a natural serum protein, 100% conserved across the mammalian class and possesses high thermal, structural and proteolytic stability. Because of its small size and lack of posttranslational modifications, it can be easily produced in Escherichia coli. In this work we provide evidence that ubiquitin is safe as tested experimentally in vivo. In contrast to previously published results, we show that, in our hands, ubiquitin does not act as a functional ligand of the chemokine receptor CXCR4. Cellular assays based on different signaling pathways of the receptor were conducted with the natural agonist SDF-1 as a benchmark. In none of the assays could a response to ubiquitin treatment be elicited. Furthermore, intravenous application to mice at high concentrations did not induce any detectable effect on cytokine levels or hematological parameters.

6-Arylcoumarins: versatile scaffolds for fluorescent sensors

6-Arylcoumarins are available as versatile scaffolds for various types of fluorescent sensors like those for cation and viscosity.