# The Structure-Activity Relationship of the Antioxidant Peptides from Natural Proteins
## 1 Introduction  
Recently, bioactive peptides have received close scientific attention for their broad scope of bioactivities, mainly including antioxidant, antihypertensive, anticancer, and antimicrobial properties. Antioxidant peptides are especially prominent for their notable contributions to human health improvement through the prevention and treatment of non-communicable chronic degenerative diseases, such as cardiovascular and cerebrovascular diseases, cancer, rheumatoid arthritis or diabetes [1]. In addition, peptides with antioxidant properties exert effective metal ion (Fe\({}^{2+}\)/Cu\({}^{2+}\)) chelating activity and lipid peroxidation inhibitory capacity, which endows them with potential properties as food processing additives. The most attractive feature of peptides is their ability to display very few side effects in humans due to their natural sources.  
It has been reported that bioactive peptides may originate from various natural proteins, such as cereals, legumes, milk, meat, egg, fish, and various marine organisms [2; 3]. In fact, the search for novel bioactive peptides has increased considerably in the last few decades. Quite rich sources of proteins, including available food commodities, processing by-products and under-utilized resources, have been used to generate these peptides [2; 4; 3]. Bioactive peptides may be released during _in vivo_ digestion, _in vitro_ enzymatic hydrolysis or food processing steps, including fermentation, germination, and ripening [2; 5]. Some results, including sources, evaluation methods, amino acid sequences and molecular weights of antioxidant peptides are listed in Table 1.  
Many efforts have been made to investigate and develop a series of methods for the enzymatic hydrolysis, isolation, purification and identification of novel peptides. Based on the recent literature, the main peptide preparation procedures are illustrated in Figure 1[6; 7; 8]. No doubt, these works have made a huge contribution towards to exploration and identification of bioactive peptides. The databases on the sequences of peptides with antioxidant capacity is gradually increasing, however, it is still difficult for researchers to know beforehand the activities of the peptides resulting from certain enzyme hydrolyses. After the repeatitious and tedious work of the above procedures, the bioactivity of peptides obtained often shows conflicting results. How can we develop an efficient strategy for designing and producing novel natural-source peptides with strong antioxidant capacity? The knowledge of underlying mechanism of the antioxidant activity is very important. Nevertheless, any successful strategy must comprehensively clarify the structure-activity relationships of antioxidant peptides, as well as the relationships of the precursor protein which releases these antioxidant sequences.  
This review was aimed at understanding and the prediction of the structure-activity relationship, and preparation of peptides with high activities more effectively. The major current knowledge and future perspectives in this field will also be discussed here.  
Figure 1: Preparation and identification of the novel antioxidant peptides from natural proteins. Note: the dotted line means that the process doesn’t always happen. The abbreviated indexes are: ORAC—Oxygen Radical Absorbance Capacity assay; TRAP—Total Radical trapping Antioxidant Parameter; TEAC—Trolox Equivalent Antioxidant Capacity; FRAP—Ferric ion-Reducing Antioxidant Power; DPPH—DiPhenyl-1-PicrylHydrozyl; CECC—Carnosine Equivalent iron Chelation Capacity; LC-MS/MS—liquid chromatography mass chromatography/mass chromatography.