Chemical Antibody Mimics Inhibit Cadherin-Mediated Cell–Cell Adhesion: A Promising Strategy for Cancer Therapy

One of the most promising strategies to treat cancer is the use of therapeutic antibodies that disrupt cell–cell adhesion mediated by dysregulated cadherins. The principal site where cell–cell adhesion occurs encompasses Trp2 found at the N-terminal region of the protein. Herein, we employed the naturally exposed highly conserved peptide Asp1-Trp2-Val3-Ile4-Pro5-Pro6-Ile7, as epitope to prepare molecularly imprinted polymer nanoparticles (MIP-NPs) to recognize cadherins. Since MIP-NPs target the site responsible for adhesion, they were more potent than commercially available therapeutic antibodies for inhibiting cell–cell adhesion in cell aggregation assays, and for completely disrupting three-dimensional tumor spheroids as well as inhibiting invasion of HeLa cells. These biocompatible supramolecular anti-adhesives may potentially be used as immunotherapeutic or sensitizing agents to enhance antitumor effects of chemotherapy.     

2,2′-Diphenyl-Δ3,3′-bi-3H-indole-1,1′-dioxide: Molecular interactions and crystal structure

The Dinitrone 2,2-diphenyl-^3,3-bi-3H-indole-1,1-dioxide acts as a demethylating and dehydrogenating agent. The mechanism of interaction of the dinitrone with donors and acceptors does not involve intermediate charge-transfer complexes probably due to a self association between dinitrone molecules (as supported by X-ray determinations). The crystal structure of the dinitrone was obtained by direct methods;a=9.967 (2),b=19.817 (3),c=10.875 (2) Å, =111.2 (2)°, space group P2₁/n. The finalR andR _w were 0.089 and 0.063 for all measured reflexes.

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2,2-Diphenyl-^3,3-bi-3H-indol-1,1-dioxid: Molekulare Wechselwirkungen und Kristallstruktur

Zusammenfassung Das Dinitron 2,2-Diphenyl-^3,3-bi-3H-indol-1,1-dioxid wirkt als Demethylierungs- und Oxydationsmittel. Die Wechselwirkung des Dinitrons mit Elektronen-Acceptoren und Elektronen-Donatoren geht wegen der Selbstassoziation zwischen den Dinitron-Molekülen ohne die dazwischenliegende Bildung eines Charge-Transfer-Komplexes vor sich; das wird auch von Röntgenstrukturuntersuchungen gestützt. Die Kristallstruktur wurde mit direkten Methoden ermittelt:a=9.967 (2),b=19.817 (3),c=10.875 (2) Å; =111.2 (2)°. P2₁/n. Die endgültigen WerteR undR _w waren 0.089 und 0.063 für alle gemessenen Reflexe.

     

Enzyme‐Initiated Free‐Radical Polymerization of Molecularly Imprinted Polymer Nanogels on a Solid Phase with an Immobilized Radical Source

An enzyme‐mediated synthetic approach is described for the preparation of molecularly imprinted polymer nanoparticles (MIP‐NPs) in aqueous media. Horseradish peroxidase (HRP) was used to initiate the polymerization of methacrylate or vinyl monomers and cross‐linkers by catalyzing the generation of free radicals. To prevent entrapment of the enzyme in the cross‐linked polymer, and to enable it to be reused, HRP was immobilized on a solid support. MIPs based on 4‐vinylpyridine and 1,4‐bis(acryloyl)piperazine for the recognition of 2,4‐dichlorophenoxyacetic acid (2,4‐D) and salicylic acid were synthesized in an aqueous medium. MIPs for the protein trypsin were also synthesized. MIP nanoparticles with sizes between 50 and 300 nm were obtained with good binding properties, a good imprinting effect, and high selectivity for the target molecule. The reusability of immobilized HRP for MIP synthesis was shown for several batches.     

Highly Efficient Synthesis and Assay of Protein‐Imprinted Nanogels by Using Magnetic Templates

We report an approach integrating the synthesis of protein‐imprinted nanogels (“plastic antibodies”) with a highly sensitive assay employing templates attached to magnetic carriers. The enzymes trypsin and pepsin were immobilized on amino‐functionalized solgel‐coated magnetic nanoparticles (magNPs). Lightly crosslinked fluorescently doped polyacrylamide nanogels were subsequently produced by high‐dilution polymerization of monomers in the presence of the magNPs. The nanogels were characterised by a novel competitive fluorescence assay employing identical protein‐conjugated nanoparticles as ligands to reversibly immobilize the corresponding nanogels. Both nanogels exhibited K_d<10 pM for their respective target protein and low cross‐reactivity with five reference proteins. This agrees with affinities reported for solid‐phase‐synthesized nanogels prepared using low‐surface‐area glass‐bead supports. This approach simplifies the development and production of plastic antibodies and offers direct access to a practical bioassay.