Abnormal Enhancement of Protein Disulfide Isomerase-like Activity of a Cyclic Diselenide Conjugated with a Basic Amino Acid by Inserting a Glycine Spacer
In a previous study, we reported that (<i>S</i>)-1,2-diselenane-4-amine (<b>1</b>) catalyzes oxidative protein folding through protein disulfide isomerase (PDI)-like catalytic mechanisms and that the direct conjugation of a basic amino acid (Xaa: His, Lys, or Arg) via an amid...
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| Autores principales: | , , |
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| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
MDPI AG
2021
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| Materias: | |
| Acceso en línea: | https://doaj.org/article/e656d5c9b25349b4972e2576a98beacb |
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| Sumario: | In a previous study, we reported that (<i>S</i>)-1,2-diselenane-4-amine (<b>1</b>) catalyzes oxidative protein folding through protein disulfide isomerase (PDI)-like catalytic mechanisms and that the direct conjugation of a basic amino acid (Xaa: His, Lys, or Arg) via an amide bond improves the catalytic activity of <b>1</b> by increasing its diselenide (Se–Se) reduction potential (<i>E</i>′°). In this study, to modulate the Se–Se redox properties and the association of the compounds with a protein substrate, new catalysts, in which a Gly spacer was inserted between <b>1</b> and Xaa, were synthesized. Exhaustive comparison of the PDI-like catalytic activities and <i>E</i>′° values among <b>1</b>, <b>1</b>-Xaa, and <b>1</b>-Gly-Xaa showed that the insertion of a Gly spacer into <b>1</b>-Xaa either did not change or slightly reduced the PDI-like activity and the <i>E</i>′° values. Importantly, however, only <b>1</b>-Gly-Arg deviated from this generality and showed obviously increased <i>E</i>°′ value and PDI-like activity compared to the corresponding compound with no Gly spacer (<b>1</b>-Arg); on the contrary, its catalytic activity was the highest among the diselenide compounds employed in this study, while this abnormal enhancement of the catalytic activity of <b>1</b>-Gly-Arg could not be fully explained by the thermodynamics of the Se–Se bond and its association ability with protein substrates. |
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