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Abstract: Here, we demonstrate a chemical modification strategy to create biomaterials of the M13 bacteriophage with extraordinary thermal stability, and high compatibility with non-aqueous ionic liquids. The results provide a blueprint for developing soft materials with well-defined architectures that may find broad applicability in the next generation of flexible devices.

Open Access

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Abstract: We present a new cell membrane modification methodology where the inherent heart tissue homing properties of the infectious bacteria Streptococcus gordonii are transferred to human stem cells. This is achieved via the rational design of a chimeric protein–polymer surfactant cell membrane binding construct, comprising the cardiac fibronectin (Fn) binding domain of the bacterial adhesin protein CshA fused to a supercharged protein. Significantly, the protein–polymer surfactant hybrid spontaneously inserts into the plasma membrane of stem cells without cytotoxicity, instilling the cells with a high affinity for immobilized fibronectin. Moreover, we show that this cell membrane reengineering approach significantly improves retention and homing of stem cells delivered either intracardially or intravenously to the myocardium in a mouse model.

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Abstract: Trichogin is a natural peptide endowed with antimicrobial and antitumor activity. A member of the peptaibol family, trichogin possesses a C‐terminal aminoalcohol. In the past, we substituted that moiety with a methyl ester for synthetic purposes and realized that this apparently slight modification causes great changes in the peptide bioactivity. Aiming at understanding the reasons behind such observations, we performed a detailed spectroscopic study on a number of trichogin analogs. In the present manuscript, we compare the data obtained from synchrotron radiation circular dichroism, NMR and fluorescence spectroscopy in organic solvents at cryogenic temperatures with those independently acquired by electron paramagnetic resonance spectroscopy at 80K. We reveal unambiguously the presence of a reversible, temperature‐driven screw‐sense interconversion from right‐handed to left‐handed helix that is determined by the C‐terminal capping moiety. Our data demonstrate for the first time the key role of a C‐terminal methyl ester in promoting peptide screw‐sense inversion.

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Abstract: Using X‐ray crystallography, we show an enantiospecificity in DNA G‐quadruplex binding, using the complexes Λ/∆‐[Ru(TAP)2(dppz‐11‐CN)]2+ (TAP=1,4,5,8‐tetraazaphenanthrene) containing the dppz (dipyridophenazine) ligand, paralleling the specificity of the complexes with duplex DNA. The Λ complex crystallises with the normally parallel stranded d(TAGGGTTA) tetraplex to give the first such antiparallel strand assembly in which syn‐guanosine is adjacent to the complex at the 5’ end of the quadruplex core. SRCD measurements confirm that the same conformational switch occurs in solution. The Δ enantiomer, by contrast, is present in the structure but stacked at the ends of the assembly. In addition, we report the structure of Λ‐[Ru(phen)2(11‐CN‐dppz)]2+ bound to d(TCGGCGCCGA), a duplex forming sequence, and use both structural models to aid in the elucidation of the motif‐specific luminescence response of the isostructural phen analogue enantiomers.

Open Access

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Abstract: Calcineurin inhibitors potentially prevent pro-allergic mediator release from basophils and mast cells but are rarely used systemically due to ubiquitous expressions of target signaling proteins. However, specific targeting of allergic effector cells with these inhibitors could circumvent unwanted side effects. We recently demonstrated the biocompatibility of gold nanoparticles (AuNPs) as a platform for non-toxic delivery of signaling inhibitors due to unique physicochemical properties of these nanomaterials. Since AuNPs can be conjugated with both anti-allergic drugs and antibodies or other proteins that specifically recognize basophils and mast cells, our aims were to assess specific targeting of allergic effector cell function using AuNPs conjugated with the calcineurin inhibitor ascomycin. Purified human basophils and LAD2 human mast cells were used for investigations with AuNPs conjugated either to CD203c antibodies or containing stem cell factor (SCF), respectively, which were amine-coupled to acidic groups of reduced glutathione (GSH). GSH was also used as a spacer for immobilization of ascomycin on the gold surface. AuNPs conjugated with anti-CD203c and ascomycin strikingly blocked IgE-dependent degranulation of both purified basophils and those present in mixed leukocyte preparations, suggesting specific targeting of these cells. In contrast, LAD2 mast cell responses were not inhibited using anti-CD203c-containing nanoconjugates but were when the conjugates contained SCF. Successful targeting of allergic effector cells using gold nanoconjugates indicates that this technology may have therapeutic potential for the treatment of allergies by specifically delivering highly effective signaling inhibitors with reduced side effects.