Poly[[chlorido-(1,10-phenanthroline-κ2N,N′)copper(II)]-μ3-1,1,3,3-tetra-cyano-2-eth-oxy-propenido- κ3N:N′:N′′] : coordination polymer sheets linked into bilayers by hydrogen bonds

The authors acknowledge the Algerian DG–RSDT (Direction Generale de la Recherche Scientifique et du Developpement Technologique) and the Algerian ATRST (Agence Thematique de Recherche en Sciences et Technologie; PNR project) for financial support. ZS thanks Sandra Lebaroud for her help in preparing the manuscript and the Unit of Support for Technical and Scientific Research (UATRS, CNRST) for the X-ray measurements.In the title compound, [Cu(C9H5N4O)Cl(C12H8N2)] n or [Cu(tcnoet)Cl(phen)] n , where phen is 1,10-phenanthroline and tcnoet is 1,1,3,3-tetra-cyano-2-eth- oxy-propenide, the axially elongated (4 + 2) coordination polyhedron around the CuII centre contains N atoms from three different tcnoet ligands. The resulting coordination polymer takes the form of sheets which are linked in pairs by a single C - H⋯N hydrogen bond to form bilayers. The bond lengths provide evidence for significant bond fixation in the phen ligand and extensive electronic delocalization in the tcnoet ligand, where the two -C(CN)2 units are rotated, in conrotatory fashion, out of the plane of the central C3O fragment.Publisher PDFPeer reviewe

Ethane-1,1,2-trisphosphonic acid hemihydrate

International audienceEthane-1,1,2-tris­phosphonic acid crystallizes as a hemihydrate, C2H9O9P3·0.5H2O, in which the water O atom lies on an inversion centre in the space group P21/c. The acid com­ponent, which contains a short but noncentred O-H...O hydrogen bond, adopts a gauche conformation. The acid components are linked by an extensive series of O-H...O hydrogen bonds to form layers, which are linked into pairs by the water mol­ecule

Demonstration of the occurrence of a non-transmembrane -helix in the extracellular loop 2 of GPR103

International audienc

Binding mode of Pyridoclax to Myeloid cell leukemia-1 (Mcl-1) revealed by Nuclear Magnetic Resonance Spectroscopy, Docking and Molecular Dynamics Approaches

International audienceMyeloid cell leukemia-1 (Mcl-1) is an anti-apoptotic member of the Bcl-2 family proteins. Its amplification is one of the most frequent genetic aberrations found in human cancers. Pyridoclax, a promising BH3 mimetic inhibitor, interacts directly with Mcl-1 and induces massive apoptosis at a concentration of 15 µM in combination with anti-Bcl-xL strategies in chemo-resistant ovarian cancer cell lines. In this study, a combined experimental and theoretical approach was used to investigate the binding mode of Pyridoclax to Mcl-1. The representative poses generated from dynamics simulations compared with NMR data revealed: (i) Pyridoclax bound to P1 and P2 pockets of Mcl-1 BH3 binding groove through its styryl and methyl groups establishing mainly hydrophobic contacts, (ii) one of the ending pyridines interacts through electrostatic interaction with K234 side chain, a negatively charged residue present only in this position in Mcl-1

Selecting the first chemical molecule inhibitor of HSP110 for colorectal cancer therapy.

Pro-survival stress-inducible chaperone HSP110 is the only HSP for which a mutation has been found in a cancer. Multicenter clinical studies demonstrated a direct association between HSP110 inactivating mutation presence and excellent prognosis in colorectal cancer patients. Here, we have combined crystallographic studies on human HSP110 and in silico modeling to identify HSP110 inhibitors that could be used in colorectal cancer therapy. Two molecules (foldamers 33 and 52), binding to the same cleft of HSP110 nucleotide-binding domain, were selected from a chemical library (by co-immunoprecipitation, AlphaScreening, Interference-Biolayer, Duo-link). These molecules block HSP110 chaperone anti-aggregation activity and HSP110 association to its client protein STAT3, thereby inhibiting STAT3 phosphorylation and colorectal cancer cell growth. These effects were strongly decreased in HSP110 knockdown cells. Foldamer's 33 ability to inhibit tumor growth was confirmed in two colorectal cancer animal models. Although tumor cell death (apoptosis) was noted after treatment of the animals with foldamer 33, no apparent toxicity was observed, notably in epithelial cells from intestinal crypts. Taken together, we identified the first HSP110 inhibitor, a possible drug-candidate for colorectal cancer patients whose unfavorable outcome is associated to HSP110