Studies from M.W. Büttner and colleagues yield new information about life sciences
2007 NOV 20 -- A new study, 'Silicon analogues of the retinoid agonists TTNPB and 3-methyl-TTNPB, disila-TTNPB and disila-3-methyl-TTNPB: chemistry and biology,' is now available. "Twofold sila-substitution (C/Si exchange) in the saturated ring of the tetrahydronaphthalene skeleton of the retinoid agonists TTNPB (1 a) and 3-methyl-TTNPB (2 a) leads to disila-TTNPB (1 b) and disila-3-methyl-TTNPB (2 b), respectively. The silicon compounds 1 b and 2 b were synthesized in multiple steps, and their identities were established by elemental analyses, multinuclear NMR experiments, and single-crystal X-ray diffraction studies," scientists in Germany report. "Like TTNPB (1 a) and 3-methyl-TTNPB (2 a), the analogous silicon-based arotinoids 1 b and 2 b are strong pan-RAR agonists and display the same strong differentiation and apoptosis-inducing activity in NB4 promyelocytic leukemia cells as the parent carbon compounds. These results are in keeping with the nearly isomorphous structures of 1 a and 1 b bound to the complex of the RARbeta ligand-binding domain with the nuclear receptor (NR) box 2 peptide of the SRC-1 coactivator. The contacts within the ligand-binding pocket are identical except for helix H11, for which two turns are shifted in the disila-TTNPB (1 b) complex," wrote M.W. Büttner and colleagues, . The researchers concluded: "This study represents the first comprehensive structure-function analysis of a carbon/silicon switch in a signaling molecule and demonstrates that silicon analogues can have the same biological functionalities and conserved structures as their parent carbon compounds, and it illustrates at the same time that silicon analogues of biologically active compounds have the potential to induce alternative allosteric effects, as in the case of helix H11, which might allow for novel options in drug design." Büttner and colleagues published their study in ChemBioChem (Silicon analogues of the retinoid agonists TTNPB and 3-methyl-TTNPB, disila-TTNPB and disila-3-methyl-TTNPB: chemistry and biology. ChemBioChem, 2007;8(14):1688-99). For additional information, contact M.W. Büttner, Universitat Wurzburg, Institut fur Anorganische Chemie, Am Hubland 97074 Wurzburg, Germany. The publisher's contact information for the journal ChemBioChem is: Wiley-V C H Verlag GmbH, PO Box 10 11 61, D-69451 Weinheim, Germany. Keywords: Germany, Life Sciences. This article was prepared by Life Science Weekly editors from staff and other reports. Copyright 2007, Life Science Weekly via NewsRx.com.
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