Anticholinesterase Inhibition, Drug-Likeness Assessment, and Molecular Docking Evaluation of Milk Protein-Derived Opioid Peptides for the Control of Alzheimer’s Disease
The drug-likeness and pharmacokinetic properties of 23 dairy-protein-derived opioid peptides were studied using SwissADME and ADMETlab in silico tools. All the opioid peptides had poor drug-like properties based on violations of Lipinski’s rule-of-five. Moreover, prediction of their pharmacokinetic...
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MDPI AG
2022-06-01
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| Series: | Dairy |
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| Online Access: | https://www.mdpi.com/2624-862X/3/3/32 |
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| author | Dawei Ji Jingying Ma Junyi Dai Min Xu Paul W. R. Harris Margaret A. Brimble Dominic Agyei |
| author_facet | Dawei Ji Jingying Ma Junyi Dai Min Xu Paul W. R. Harris Margaret A. Brimble Dominic Agyei |
| author_sort | Dawei Ji |
| collection | DOAJ |
| description | The drug-likeness and pharmacokinetic properties of 23 dairy-protein-derived opioid peptides were studied using SwissADME and ADMETlab in silico tools. All the opioid peptides had poor drug-like properties based on violations of Lipinski’s rule-of-five. Moreover, prediction of their pharmacokinetic properties showed that the peptides had poor intestinal absorption and bioavailability. Following this, two well-known opioid peptides (β<sub>b</sub>-casomorphin-5, β<sub>b</sub>-casomorphin-7) from A1 bovine milk and caffeine (positive control) were selected for in silico molecular docking and in vitro inhibition study with two cholinesterase enzyme receptors important for the pathogenesis of Alzheimer’s disease. Both peptides showed higher binding free energies and inhibitory activities to butyrylcholinesterase (BChE) than caffeine, but in vitro binding energy values were lower than those from the docking model. Moreover, the two casomorphins had lower inhibitory properties against acetylcholinesterase (AChE) than caffeine, although the docking model predicted the opposite. At 1 mg/mL concentrations, β<sub>b</sub>-casomorphin-5 and β<sub>b</sub>-casomorphin-7 showed promising results in inhibiting both cholinesterases (i.e., respectively 34% and 43% inhibition of AChE, and 67% and 81% inhibition of BChE). These dairy-derived opioid peptides have the potential to treat Alzheimer’s disease via cholinesterase inhibition. However, appropriate derivatization may be required to improve their poor predicted intestinal absorption and bioavailability. |
| first_indexed | 2024-03-10T00:19:04Z |
| format | Article |
| id | doaj.art-894335f97b88474ba669881a4f39a707 |
| institution | Directory Open Access Journal |
| issn | 2624-862X |
| language | English |
| last_indexed | 2024-03-10T00:19:04Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Dairy |
| spelling | doaj.art-894335f97b88474ba669881a4f39a7072023-11-23T15:46:21ZengMDPI AGDairy2624-862X2022-06-013342243710.3390/dairy3030032Anticholinesterase Inhibition, Drug-Likeness Assessment, and Molecular Docking Evaluation of Milk Protein-Derived Opioid Peptides for the Control of Alzheimer’s DiseaseDawei Ji0Jingying Ma1Junyi Dai2Min Xu3Paul W. R. Harris4Margaret A. Brimble5Dominic Agyei6Department of Food Science, University of Otago, Dunedin 9054, New ZealandDepartment of Food Science, University of Otago, Dunedin 9054, New ZealandDepartment of Management, University of Otago, Dunedin 9054, New ZealandDepartment of Food Science, University of Otago, Dunedin 9054, New ZealandSchool of Biological Sciences, The University of Auckland, Auckland 1142, New ZealandSchool of Biological Sciences, The University of Auckland, Auckland 1142, New ZealandDepartment of Food Science, University of Otago, Dunedin 9054, New ZealandThe drug-likeness and pharmacokinetic properties of 23 dairy-protein-derived opioid peptides were studied using SwissADME and ADMETlab in silico tools. All the opioid peptides had poor drug-like properties based on violations of Lipinski’s rule-of-five. Moreover, prediction of their pharmacokinetic properties showed that the peptides had poor intestinal absorption and bioavailability. Following this, two well-known opioid peptides (β<sub>b</sub>-casomorphin-5, β<sub>b</sub>-casomorphin-7) from A1 bovine milk and caffeine (positive control) were selected for in silico molecular docking and in vitro inhibition study with two cholinesterase enzyme receptors important for the pathogenesis of Alzheimer’s disease. Both peptides showed higher binding free energies and inhibitory activities to butyrylcholinesterase (BChE) than caffeine, but in vitro binding energy values were lower than those from the docking model. Moreover, the two casomorphins had lower inhibitory properties against acetylcholinesterase (AChE) than caffeine, although the docking model predicted the opposite. At 1 mg/mL concentrations, β<sub>b</sub>-casomorphin-5 and β<sub>b</sub>-casomorphin-7 showed promising results in inhibiting both cholinesterases (i.e., respectively 34% and 43% inhibition of AChE, and 67% and 81% inhibition of BChE). These dairy-derived opioid peptides have the potential to treat Alzheimer’s disease via cholinesterase inhibition. However, appropriate derivatization may be required to improve their poor predicted intestinal absorption and bioavailability.https://www.mdpi.com/2624-862X/3/3/32casomorphinsopioid peptidescholinesterase inhibitorsmolecular dockingbioinformaticsAlzheimer’s disease |
| spellingShingle | Dawei Ji Jingying Ma Junyi Dai Min Xu Paul W. R. Harris Margaret A. Brimble Dominic Agyei Anticholinesterase Inhibition, Drug-Likeness Assessment, and Molecular Docking Evaluation of Milk Protein-Derived Opioid Peptides for the Control of Alzheimer’s Disease Dairy casomorphins opioid peptides cholinesterase inhibitors molecular docking bioinformatics Alzheimer’s disease |
| title | Anticholinesterase Inhibition, Drug-Likeness Assessment, and Molecular Docking Evaluation of Milk Protein-Derived Opioid Peptides for the Control of Alzheimer’s Disease |
| title_full | Anticholinesterase Inhibition, Drug-Likeness Assessment, and Molecular Docking Evaluation of Milk Protein-Derived Opioid Peptides for the Control of Alzheimer’s Disease |
| title_fullStr | Anticholinesterase Inhibition, Drug-Likeness Assessment, and Molecular Docking Evaluation of Milk Protein-Derived Opioid Peptides for the Control of Alzheimer’s Disease |
| title_full_unstemmed | Anticholinesterase Inhibition, Drug-Likeness Assessment, and Molecular Docking Evaluation of Milk Protein-Derived Opioid Peptides for the Control of Alzheimer’s Disease |
| title_short | Anticholinesterase Inhibition, Drug-Likeness Assessment, and Molecular Docking Evaluation of Milk Protein-Derived Opioid Peptides for the Control of Alzheimer’s Disease |
| title_sort | anticholinesterase inhibition drug likeness assessment and molecular docking evaluation of milk protein derived opioid peptides for the control of alzheimer s disease |
| topic | casomorphins opioid peptides cholinesterase inhibitors molecular docking bioinformatics Alzheimer’s disease |
| url | https://www.mdpi.com/2624-862X/3/3/32 |
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