QSAR Study on Antioxidant Tripeptides and the Antioxidant Activity of the Designed Tripeptides in Free Radical Systems

Abstract

In this study, quantitative structure-activity relationship (QSAR) models were determined based on 91 antioxidant tripeptides. We firstly adopted the stepwise regression (SWR) method for selecting key variables without autocorrelation and then utilized multiple linear regression (MLR), support vector machine (SVM), random forest (RF), and partial least square regression (PLS) to develop predictive QSAR models based on the screened variables. The results demonstrated that all the established models have good reliability (R2train > 0.86, Q2train > 0.70) and relatively good predictability (R2test > 0.88). The contribution of amino acid residues was calculated from the stepwise regression combined with multiple linear regression (SWR-MLR) method model that shows Trp, Tyr, or Cys at C-terminus is favorable for antioxidant activity of tripeptides. Nineteen antioxidant tripeptides were designed based on SWR-MLR models, and the antioxidant activity of these tripeptides were evaluated using three antioxidant assays in free radical systems (1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging capacity, trolox equivalent antioxidant capacity assay, and the ferric reducing antioxidant power assay). The experimental antioxidant activities of these tripeptides were higher than the calculated/predicted activity values of the QSAR models. The QSAR models established can be used to identify and screen novel antioxidant tripeptides with high activity.

Quantitative analysis of the relationship between structure and antioxidant activity of tripeptides

“…Furthermore, they indicated that amino acids having high oxidative susceptibility were those containing nucleophilic sulfur‐containing side chains such as Cys or aromatic side chains such as Trp, Tyr, Phe, and His . Recently, it was also reported using different QSAR models that Trp, Tyr, or Cys at C‐terminus is favorable for antioxidant activity of tripeptides . On the contrary, in previously reported antioxidant peptides, cysteine was found less frequently as one of the constituent amino acids .…”

Quantitative Structure-Activity Relationship Study of Antioxidant Tripeptides Based on Model Population Analysis

“…Our results are in agreement with the previous findings that most of the important variables that were selected by BOSS originated from the N-terminus or C-terminus ( Figure 2 and Figure 3 B). In addition, studies showed that tripeptides containing Cys (C), Trp (W), and Tyr (Y) residues exhibited strong antioxidant activities [ 8 , 10 ]. Tripeptides YHY and LTC, for the two datasets, respectively, having the highest antioxidant activities is confirmed by our study.…”

“…Quantitative structure-activity relationship (QSAR), which is a well-recognized tool for estimating chemical activities, has been widely applied for bioactive peptides prediction [ 5 ]. The QSAR models have been successfully built on ACE-inhibitory peptides [ 6 ], antimicrobial peptides [ 7 ], antioxidant peptides [ 8 , 9 , 10 ], antitumor peptides [ 11 ], bitter peptides [ 12 ], and etc. The QSAR study of antioxidant peptides mainly focused on di and tripeptides, because they can be absorbed intact from the intestinal lumen into the bloodstream and then produce biological effects at the tissue level [ 13 ].…”

Synthesis, characterization, antimicrobial activity, 3D‐QSAR, DFT, and molecular docking of some ciprofloxacin derivatives and their copper(II) complexes

“…QSAR modeling is one of the most suitable approaches for the prediction and validation of applicable quantitative properties. [ 40 ] Previous studies identified some quinolone derivatives as potent antibiotics. As determined from the technique of model construction, the compounds were divided into a training class (80%) and a test class (about 20%) of quinolones.…”