Mechanistic Studies of Electrode-Assisted Catalytic Oxidation by Flavinium and Acridinium Cations

Electrochemical behavior of flavinium (Et-Fl⁺) and acridinium (Acr⁺) cations is presented, in order to investigate their activity toward catalytic water oxidation. Cyclic voltammograms of Acr⁺ and Et-Fl⁺ in acetonitrile are qualitatively similar, with oxidation peaks at highly positive potentials, and these oxidation peaks depend strongly on the type of the working electrode being used. However, the two model compounds exhibit different behaviors in the presence of water: while Et-Fl⁺ facilitates electrocatalytic water oxidation through an electrode-assisted mechanism, water oxidation is not accelerated in the presence of Acr⁺. A comparative study of variable scan-rate cyclic voltammetry, concentration dependence, and spectroelectrochemical behavior of two model compounds suggest that Et-Fl⁺ and Acr⁺ exhibit different reaction pathways with the electrode surface. On the basis of the experimental results, a mechanism is proposed to account for the observed differences in electrocatalysis

Structure-Based Optimization of a Peptidyl Inhibitor against Calcineurin-Nuclear Factor of Activated T Cell (NFAT) Interaction

Calcineurin inhibitors such as cyclosporine A and FK506 are effective immunosuppressants but produce severe side effects. Rational modification of a previously reported peptide inhibitor, GPHPVIVITGPHEE (<i>K</i>_D ∼ 500 nM), by replacing the two valine residues with <i>tert</i>-leucine and the C-terminal proline with a <i>cis</i>-proline analogue, gave an improved inhibitor ZIZIT-<i>cis</i>Pro, which binds to calcineurin with a <i>K</i>_D value of 2.6 nM and is more resistant to proteolysis