6 research outputs found

    Inversion domains in AlN grown on (0001) sapphire

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    Al-polarity inversion domains formed during AlN layer growth on (0001) sapphire were identified using transmission electron microscopy (TEM). They resemble columnar inversion domains reported for GaN films grown on (0001) sapphire. However, for AlN, these columns have a V-like shape with boundaries that deviate by 2 {+-} 0.5{sup o} from the c-axis. TEM identification of these defects agrees with the post-growth surface morphology as well as with the microstructure revealed by etching in hot aqueous KOH

    Argyrin B a non-competitive inhibitor of the human immunoproteasome exhibiting preference for β1i

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    Inhibitors of the proteasome have found broad therapeutic applications however, they show severe toxicity due to the abundance of proteasomes in healthy cells. In contrast, inhibitors of the immunoproteasome, which is upregulated during disease states, are less toxic and have increased therapeutic potential including against autoimmune disorders. In this project, we report argyrin B, a natural product cyclic peptide to be a reversible, non-competitive inhibitor of the immunoproteasome. Argyrin B showed selective inhibition of the β5i and β1i sites of the immunoproteasome over the β5c and β1c sites of the constitutive proteasome with nearly 20-fold selective inhibition of β1i over the homologous β1c. Molecular modelling attributes the β1i over β1c selectivity to the small hydrophobic S1 pocket of β1i and β5i over β5c to site-specific amino acid variations that enable additional bonding interactions and stabilization of the binding conformation. These findings facilitate the design of immunoproteasome selective and reversible inhibitors that may have a greater therapeutic potential and lower toxicity

    Positioning of proteasome inhibitors in therapy of solid malignancies

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