| Title : Molecular Mechanistic Insights into Dipeptidyl Peptidase-IV Inhibitory Peptides to Decipher the Structural Basis of Activity - Wang_2024_J.Agric.Food.Chem_72_11230 |
| Author(s) : Wang C , Zheng L , Udenigwe CC , Lin L , Zhao M |
| Ref : Journal of Agricultural and Food Chemistry , 72 :11230 , 2024 |
| Abstract : Dipeptidyl peptidase-IV (DPP-IV) inhibiting peptides have attracted increased attention because of their possible beneficial effects on glycemic homeostasis. However, the structural basis underpinning their activities has not been well understood. This study combined computational and in vitro investigations to explore the structural basis of DPP-IV inhibitory peptides. We first superimposed the Xaa-Pro-type peptide-like structures from several crystal structures of DPP-IV ligand-protein complexes to analyze the recognition interactions of DPP-IV to peptides. Thereafter, a small set of Xaa-Pro-type peptides was designed to explore the effect of key interactions on inhibitory activity. The intramolecular interaction of Xaa-Pro-type peptides at the first and third positions from the N-terminus was pivotal to their inhibitory activities. Residue interactions between DPP-IV and residues of the peptides at the fourth and fifth positions of the N-terminus contributed significantly to the inhibitory effect of Xaa-Pro-type tetrapeptides and pentapeptides. Based on the interaction descriptors, quantitative structure-activity relationship (QSAR) studies with the DPP-IV inhibitory peptides resulted in valid models with high R(2) values (0.90 for tripeptides; 0.91 for tetrapeptides and pentapeptides) and Q(2) values (0.33 for tripeptides; 0.68 for tetrapeptides and pentapeptides). Taken together, the structural information on DPP-IV and peptides in this study facilitated the development of novel DPP-IV inhibitory peptides. |
| ESTHER : Wang_2024_J.Agric.Food.Chem_72_11230 |
| PubMedSearch : Wang_2024_J.Agric.Food.Chem_72_11230 |
| PubMedID: 38709903 |
| Title : Quantitative Structure-Activity Relationship Modeling of Pea Protein-Derived Acetylcholinesterase and Butyrylcholinesterase Inhibitory Peptides - Asen_2023_J.Agric.Food.Chem__ |
| Author(s) : Asen ND , Udenigwe CC , Aluko RE |
| Ref : Journal of Agricultural and Food Chemistry , : , 2023 |
| Abstract : The aim of this work was to determine the structural requirements for peptides that inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activities. The data set used consisted of 19 oligopeptides that had been identified through mass spectrometry analysis of enzymatic digests of yellow field pea protein. The structure-function relationship was analyzed by partial least squares regression using the 5z scores. A nine-component model was created from 16 peptides for AChE inhibitory peptides (Q(2) = 67.2% and R(2) = 0.9974), while three data sets were prepared for BuChE inhibitory peptides to improve the quality of the models (Q(2) = 26.7-46.4% and R(2) = 0.9577-0.9958). The most active peptides from the PLS models have threonine, leucine, alanine, and valine at the N terminal, asparagine, histidine, proline, and arginine at the second position, with aspartic acid and serine at the third, and arginine at the C terminal. |
| ESTHER : Asen_2023_J.Agric.Food.Chem__ |
| PubMedSearch : Asen_2023_J.Agric.Food.Chem__ |
| PubMedID: 37856319 |
| Title : In vitro inhibition of acetylcholinesterase activity by yellow field pea (Pisum sativum) protein-derived peptides as revealed by kinetics and molecular docking - Asen_2022_Front.Nutr_9_1021893 |
| Author(s) : Asen ND , Okagu OD , Udenigwe CC , Aluko RE |
| Ref : Front Nutr , 9 :1021893 , 2022 |
| Abstract : Compounds with structural similarities to the neurotransmitter (acetylcholine) are mostly used to inhibit the activity of acetylcholinesterase (AChE) in Alzheimer's disease (AD) therapy. However, the existing drugs only alleviate symptoms of moderate to mild conditions and come with side effects; hence, the search is still on for potent and safer options. In this study, High performance liquid chromatography (HPLC) fractionations of AChE-inhibitory pea protein hydrolysates obtained from alcalase, flavourzyme and pepsin digestions were carried out followed by sequence identification of the most active fractions using mass spectrometry. Subsequently, 20 novel peptide sequences identified from the active fractions were synthesized and five peptides, QSQS, LQHNA, SQSRS, ETRSQ, PQDER (IC(50) = 1.53 - 1.61 microg/mL) were selected and analyzed for ability to change AChE protein conformation (fluorescence emission and circular dichroism), kinetics of enzyme inhibition, and enzyme-ligand binding configurations using molecular docking. The kinetics studies revealed different inhibition modes by the peptides with relatively low (<0.02 mM and <0.1 mM) inhibition constant and Michaelis constant, respectively, while maximum velocity was reduced. Conformational changes were confirmed by losses in fluorescence intensity and reduced alpha-helix content of AChE after interactions with different peptides. Molecular docking revealed binding of the peptides to both the catalytic anionic site and the peripheral anionic site. The five analyzed peptides all contained glutamine (Q) but sequences with Q in the penultimate N-terminal position (LQHNA, SQSRS, and PQDER) had stronger binding affinity. Results from the different analysis in this study confirm that the peptides obtained from enzymatic digestion of pea protein possess the potential to be used as novel AChE-inhibitory agents in AD management. |
| ESTHER : Asen_2022_Front.Nutr_9_1021893 |
| PubMedSearch : Asen_2022_Front.Nutr_9_1021893 |
| PubMedID: 36337665 |