- Self-Assembly and Molecular Recognition in Water: Tubular Stacking and Guest-Templated Discrete Assembly of Water-Soluble, Shape-Persistent Macrocycles
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Supramolecular chemistry in aqueous media is an area with great fundamental and practical significance. To examine the role of multiple noncovalent interactions in controlled assembling and binding behavior in water, the self-association of five water-soluble hexakis(m-phenylene ethynylene) (m-PE) macrocycles, along with the molecular recognition behavior of the resultant assemblies, is investigated with UV-vis, fluorescence, CD, and NMR spectroscopy, mass spectrometry, and computational studies. In contrast to their different extents of self-aggregation in organic solvents, all five macrocycles remain aggregated in water at concentrations down to the micromolar (μM) range. CD spectroscopy reveals that 1-F6 and 1-H6, two macrocycles carrying chiral side chains and capable of H-bonded self-association, assemble into tubular stacks. The tubular stacks serve as supramolecular hosts in water, as exemplified by the interaction of macrocycles 1-H6 and 2-H6 and guests G1 through G4, each having a rod-like oligo(p-phenylene ethynylene) (p-PE) segment flanked by two hydrophilic chains. Fluorescence and 1H NMR spectroscopy revealed the formation of kinetically stable, discrete assemblies upon mixing 2-H6 and a guest. The binding stoichiometry, determined with fluorescence, 1H NMR, and ESI-MS, reveals that the discrete assemblies are novel pseudorotaxanes, each containing a pair of identical guest molecules encased by a tubular stack. The two guest molecules define the number of macrocyclic molecules that comprise the host, which curbs the "infinite" stack growth, resulting in a tubular stack with a cylindrical pore tailoring the length of the p-PE segment of the bound guests. Each complex is stabilized by the action of multiple noncovalent forces including aromatic stacking, side-chain H-bonding, and van der Waals interactions. Thus, the interplay of multiple noncovalent forces aligns the molecules of macrocycles 1 and 2 into tubular stacks with cylindrical inner pores that, upon binding rod-like guests, lead to tight, discrete, and well-ordered tubular assemblies that are unprecedented in water.
- Wang, Qiuhua,Zhong, Yulong,Miller, Daniel P.,Lu, Xiaoxing,Tang, Quan,Lu, Zhong-Lin,Zurek, Eva,Liu, Rui,Gong, Bing
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p. 2915 - 2924
(2020/02/04)
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- Targeting G Protein-Coupled Receptors with Magnetic Carbon Nanotubes: The Case of the A3 Adenosine Receptor
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The A3 adenosine receptor (AR) is a G protein-coupled receptor (GPCR) overexpressed in the membrane of specific cancer cells. Thus, the development of nanosystems targeting this receptor could be a strategy to both treat and diagnose cancer. Iron-filled carbon nanotubes (CNTs) are an optimal platform for theranostic purposes, and the use of a magnetic field can be exploited for cancer magnetic cell sorting and thermal therapy. In this work, we have conjugated an A3AR ligand on the surface of iron-filled CNTs with the aim of targeting cells overexpressing A3ARs. In particular, two conjugates bearing PEG linkers of different length were designed. A docking analysis of A3AR showed that neither CNT nor linker interferes with ligand binding to the receptor; this was confirmed by in vitro preliminary radioligand competition assays on A3AR. Encouraged by this result, magnetic cell sorting was applied to a mixture of cells overexpressing or not the A3AR in which our compound displayed indiscriminate binding to all cells. Despite this, it is the first time that a GPCR ligand has been anchored to a magnetic nanosystem, thus it opens the door to new applications for cancer treatment.
- Pineux, Florent,Federico, Stephanie,Klotz, Karl-Norbert,Kachler, Sonja,Michiels, Carine,Sturlese, Mattia,Prato, Maurizio,Spalluto, Giampiero,Moro, Stefano,Bonifazi, Davide
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p. 1909 - 1920
(2020/09/11)
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- AMYLOID TARGETING AGENTS AND METHODS OF USING THE SAME
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Provided herein is the design and synthesis of novel molecular rotor fluorophores useful for detection of amyloid or amyloid like proteins. The fluorophores are designed to exhibit enhanced fluorescence emission upon associating with amyloid or amyloid like proteins as compared to unbound compound. Also disclosed herein are methods for treating diseases associated with amyloid or amyloid like proteins.
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- IN VITRO COMPOSITIONS COMPRISING HUMAN SAMPLE AND AMYLOID TARGETING AGENT
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Provided herein are compositions and methods useful for detection of amyloid related disorders in samples, such as human tissue, cell or body fluid. Use of the compositions and methods herein allows for the rapid, in vitro detection of amyloid accumulation, often before amyloid disorder symptoms are manifest or without introduction of foreign fluorophore molecules into a subject.
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- AMYLOID TARGETING AGENTS AND METHODS OF USING THE SAME
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Provided herein is the design and synthesis of novel molecular rotor fluorophores useful for detection of amyloid or amyloid like proteins. The fluorophores are designed to exhibit enhanced fluorescence emission upon associating with amyloid or amyloid like proteins as compared to unbound compound. Also disclosed herein are the methods for treating of diseases associated with an amyloid or amyloid like proteins.
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- Designed Intercalators for Modification of DNA Origami Surface Properties
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The modification of the backbone properties of DNA origami nanostructures through noncovalent interactions with designed intercalators, based on acridine derivatized with side chains containing esterified fatty acids or oligo(ethylene glycol) residues is reported. Spectroscopic analyses indicate that these intercalators bind to DNA origami structures. Atomic force microscopy studies reveal that intercalator binding does not affect the structural intactness but leads to altered surface properties of the highly negatively charged nanostructures, as demonstrated by their interaction with solid mica or graphite supports. Moreover, the noncovalent interaction between the intercalators and the origami structures leads to alteration in cellular uptake, as shown by confocal microscopy studies using two different eukaryotic cell lines. Hence, the intercalator approach offers a potential means for tailoring the surface properties of DNA nanostructures. Into the fold: Designed acridine derivatives bearing esterified fatty acids or oligo-ethyleneglycol side chains (see figure) can be used to alter the surface properties of DNA origami nanostructures. Noncovalent binding of the intercalators changes the interaction of the origami with solid supports and the membrane of living cells. HOPG=highly oriented pyrolytic graphite.
- Brglez, Josipa,Nikolov, Pavel,Angelin, Alessandro,Niemeyer, Christof M.
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p. 9440 - 9446
(2015/06/30)
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- New derivatives of resveratrol
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A novel class of derivatives of resveratrol is provided which have favourable physico-chemical properties when compared with resveratrol itself. It is characterized by the presence of three carbamate functions, in which resveratrol is the oxygen-linked moiety, while the nitrogen atom carries a substituent conferring desirable characteristics to the molecule. These new compounds are especially suitable as precursors (prodrugs) and vehicles of resveratrol in preparations used as dietary integrators or in pharmaceutical compositions: they are stable towards oxidative degradation allowing for long shelf lifetimes and have suitable reactivity to regenerate and deliver resveratrol under physiological conditions.
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- Amphiphilic polyene macrolide antibiotic compounds
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Described herein is a method, and the resulting compound, for the synthesis of improved amphiphilic antibiotic agents achieved by altering the chemical structure of amphiphilic polyene macrolide compounds with an oligo(ethylene glycol) conjugate in order to raise the critical micelle concentration of the compound.
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- Nonionic Amphiphilic Compounds from Lysine as Molecular Mimics of Lecithins
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New monodisperse nonionic surfactant molecules, based on lysine with two fatty acid chains in the hydrophobic part and one or two polyoxoethylene methoxycapped chains (EOn-Me) in the hydrophilic headgroup, are synthesized as mimics of natural lecithins.Their surface-activity properties indicate that these compounds have surfactant behavior whose global hydrophobic contribution is comparable to that of one fatty chain. - Key Words: Amphiphilic compounds; critical micelle concentration; mimics of lecithins; surface tension
- Seguer, J.,Selve, C.,Allouch, M.,Infante, M. R.
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- Micelle/monomer control over the membrane-disrupting properties of an amphiphilic antibiotic
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A homologous series of amphotericin B-oligo(ethylene glycol) conjugates has been synthesized, via condensation of the carboxylic acid group of amphotericin B with oligo(ethylene glycol)-substituted amines [NH2(CH2-CH2O)(n)CH3, where n = 1, 6, 15], and examined with respect to their aggregation properties and their ability to disrupt the membrane integrity of Candida albicans and human red blood cells. Incremental increase in the size of the oligo(ethylene glycol) moiety leads to a significant increase in the critical micelle concentration of the macrolide and to a corresponding increase in the concentration that is required for hemolysis. In sharp contrast, the same increase in oligo(ethylene glycol) size affords only a modest reduction in antifungal activity; the net result is a separation of antifungal and hemolytic activity. These results clearly highlight the need for taking into account the aggregation properties of membrane-disrupting antibiotics with respect to target recognition and specificity and also with regard to rational molecular design.
- Yamashita, Keiji,Janout, Vaclav,Bernard, Edward M.,Armstrong, Donald,Regen, Steven L.
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p. 6249 - 6253
(2007/10/02)
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