| Autor: |
Parkman JA; Department of Chemistry and Biochemistry, Brigham Young University, Provo, Utah 84602, United States., Barlow CD; Department of Chemistry and Biochemistry, Brigham Young University, Provo, Utah 84602, United States., Sheppert AP; Department of Chemistry and Biochemistry, Brigham Young University, Provo, Utah 84602, United States., Jacobsen S; Department of Chemistry and Biochemistry, Brigham Young University, Provo, Utah 84602, United States., Barksdale CA; Department of Chemistry and Biochemistry, Brigham Young University, Provo, Utah 84602, United States., Wayment AX; Department of Chemistry and Biochemistry, Brigham Young University, Provo, Utah 84602, United States., Newton MP; Department of Chemistry and Biochemistry, Brigham Young University, Provo, Utah 84602, United States., Burt SR; Department of Chemistry and Biochemistry, Brigham Young University, Provo, Utah 84602, United States., Michaelis DJ; Department of Chemistry and Biochemistry, Brigham Young University, Provo, Utah 84602, United States. |
| Abstrakt: |
Proteins and enzymes generally achieve their functions by creating well-defined 3D architectures that pre-organize reactive functionalities. Mimicking this approach to supramolecular pre-organization is leading to the development of highly versatile artificial chemical environments, including new biomaterials, medicines, artificial enzymes, and enzyme-like catalysts. The use of β-turn and α-helical motifs is one approach that enables the precise placement of reactive functional groups to enable selective substrate activation and reactivity/selectivity that approaches natural enzymes. Our recent work has demonstrated that helical peptides can serve as scaffolds for pre-organizing two reactive groups to achieve enzyme-like catalysis. In this study, we used CYANA and AmberTools to develop a computational approach for determining how the structure of our peptide catalysts can lead to enhancements in reactivity. These results support our hypothesis that the bifunctional nature of the peptide enables catalysis by pre-organizing the two catalysts in reactive conformations that accelerate catalysis by proximity. We also present evidence that the low reactivity of monofunctional peptides can be attributed to interactions between the peptide-bound catalyst and the helical backbone, which are not observed in the bifunctional peptide. |
