LAUSR

The red tree frog Litoria rubella from Australia has been studied for several decades showing that their dorsal skin glands secrete a number of small peptides containing a Pro–Trp sequence, known as tryptophyllin L peptides. Although peptides from many genera of Australian frogs have been reported to possess a variety of biological activities, the bioactivities of this peptide family have remained to be discovered. In this study, we investigated the antioxidant potency of a number of tryptophyllin L peptides for the first time using a joint statistical and experimental approach in which predictions based on Gaussian three‐dimensional quantitative structure–activity relationship (3D‐QSAR) models were employed to guide an in vitro experimental investigation. Two tryptophyllin tripeptides P–W–L (OH) and P–W–L (NH2) were predicted to have the Trolox equivalent antioxidant capacity (TEAC) values of 0.80 and 0.87 μM Trolox/μM peptide, respectively. With those promising results, antioxidant capabilities of five tryptophyllin L peptides with the common core Pro–Trp–Leu were synthesized and subjected to 1,1‐diphenyl‐2‐picrylhydrazyl (DPPH), ferric reducing ability of plasma (FRAP) and 2,2′‐azino‐bis(3‐ethylbenzothiazoline‐6‐sulphonic acid) radical cation (ABTS˙+) radical scavenging assays. The tests indicated that all the tested tryptophyllin L peptides, noticeably S–P–W–L (OH) and F–P–W–L (NH2), are strong ABTS˙+ radical scavengers and moderate scavengers in the other two assays. The results, thus, suggested that the tryptophyllin L peptides are likely to be a part of the skin antioxidant system helping the frog to cope with drastic change in oxygen exposure and humidity, as they inhabit over a large area of Australia with a wide climate variation.