Abstract
The glycosidase α-amylase is responsible for the hydrolysis of α(1→4) glycosidic linkages found in dietary starch as one means for controlling blood sugar level. The effect of α-amylase is detrimental, however, in the disease state diabetes mellitus, where blood glucose levels are elevated due to a biochemical defect. Inhibition of the enzyme's activity would reduce glucose absorption by the small intestine. Our objective was to develop small peptides based on essential binding elements of the natural protein inhibitor, Tendamistat. These smaller analogs may be better studied structurally and conformationally to help us understand molecular-level interactions. In addition, we have been able to correlate the activity of our compounds with the lowest unoccupied molecular orbital (LUMO) localization in energy-minimized conformations. The positive charge/LUMO of most active inhibitors is localized on the central Arg residue of the required triplet. This provides a predictive model for the design of active molecules.
Original language | English |
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Pages (from-to) | 4262-4268 |
Number of pages | 7 |
Journal | Bioorganic and Medicinal Chemistry |
Volume | 13 |
Issue number | 13 |
DOIs | |
State | Published - Jul 1 2005 |
Keywords
- Inhibitor
- Peptide
- Tendamistat
- α-Amylase