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    Synthetic Aminopyrrolic Receptors have Apoptosis Inducing Activity

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    2015_Park.pdf (1.924Mb)
    Date
    2015-09
    Author
    Park, Seong-Hyun
    Choi, Yoon Pyo
    Park, Jihong
    Share, Andrew
    Francesconi, Oscar
    Nativi, Cristina
    Namkung, Wan
    Sessler, Jonathan L.
    Roelens, Stefano
    Shin, Injae
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    Abstract
    We report two synthetic aminopyrrolic compounds that induce apoptotic cell death. These compounds have been previously shown to act as receptors for mannosides. The extent of receptor-induced cell death is greater in cells expressing a high level of high-mannose oligosaccharides than in cells producing lower levels of high-mannose glycans. The ability of synthetic receptors to induce cell death is attenuated in the presence of external mannosides. The present results provide support for the suggestion that the observed cell death reflects an ability of the receptors to bind mannose displayed on the cell surface. Signaling pathway studies indicate that the synthetic receptors of the present study promote JNK activation, induce Bax translocation to the mitochondria, and cause cytochrome c release from the mitochondria into the cytosol, thus promoting caspase-dependent apoptosis. Such effects are also observed in cells treated with mannose-binding ConA. The present results thus serve to highlight what may be an attractive new approach to triggering apoptosis via modes of action that differ from those normally used to promote apoptosis.
    Department
    Chemistry
    Subject
    programmed cell-death
    mannose-binding
    small-molecule
    concanavalin-a
    plant-lectins
    u937 cells
    in-vitro
    pradimicin
    proteins
    agents
    chemistry, multidisciplinary
    URI
    http://hdl.handle.net/2152/41160
    Citation
    Park, Seong-Hyun, Yoon Pyo Choi, Jinhong Park, Andrew Share, Oscar Francesconi, Cristina Nativi, Wan Namkung, Jonathan L. Sessler, Stefano Roelens, and Injae Shin. "Synthetic aminopyrrolic receptors have apoptosis inducing activity." Chemical Science 6, no. 12 (Sep., 2015): 7284-7292.
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