Abstract
β-lactoglobulin (β-LG) is a pivotal nutritional and functional protein. However, its application is limited by its antigenicity and susceptibility to oxidation. Here, we explore the impact of covalent modification by six natural compounds on the antigenicity and antioxidant characteristics of β-LG to explore the underlying interaction mechanism. Our findings reveal that the covalent interaction of β-LG and flavonoids reduces the antigenicity of β-LG, with the following inhibition rates: epigallocatechin-3-gallate (EGCG) (57.0%), kaempferol (42.4%), myricetin (33.7%), phloretin (28.6%), naringenin (26.7%), and quercetin (24.3%). Additionally, the β-LG-flavonoid conjugates exhibited superior antioxidant capacity compared to natural β-LG. Our results demonstrate that the significant structural modifications from α-helix to β-sheet induced by flavonoid conjugation elicited distinct variations in the antigenicity and antioxidant activity of β-LG. Therefore, the conjugation of β-LG with flavonoids presents a prospective method to reduce the antigenicity and enhance the antioxidant capacity of β-LG.