ROLE OF FOOD PROTEIN-DERIVED ZINC-CHELATING PEPTIDES IN HUMAN NUTRITION AND INFLAMMATION

Abstract

Food protein-derived peptides possess the intrinsic capacity to form metal complexes, notably physiologically relevant metals such as Zn2+. The Zn2+-binding property of peptides can be exploited to enhance human zinc bioavailability, as dietary Zn2+ can be delivered in form of zinc-peptide complexes. Effective zinc delivery through peptides depends on the gastrointestinal stability of the complexes and zinc release for absorption, which in turn can be influenced by the structural properties, such as net surface charge, of the peptides. An integral study in this project investigated the influence of the structural properties of whey protein hydrolysates produced with Everlase (WPH-Ever) and papain (WPH-Pap) on the gastric stability and dialyzability of their zinc complexes. WPH-Ever had higher zinc-chelating capacity than WPH-Pap due to its higher net negative charge. Moreover, the zinc complex of WPH-Ever was more stable during simulated gastric digestion, which can be attributed to its more negatively charged surface, leading to the formation of stronger zinc complexes. However, the higher zinc-binding of WPH-Ever resulted in lesser total zinc dialyzability, whereas more zinc ions were released from WPH-Pap; this suggests that peptides’ structures can affect the stability of their zinc complexes and zinc accessibility. Zinc-chelating food peptides have the potential to inactivate the zinc-dependent endopeptidase “a disintegrin and metalloproteinase 17” (ADAM17), which is responsible for the release of tumour necrosis factor-α (TNF-α), a therapeutic target in inflammatory diseases. Zinc-chelating peptides derived from whey and rye secalin proteins inhibited ADAM17 enzymatic activity up to 93 and 70%, respectively. Moreover, the secalin peptides quenched ADAM17 fluorescence emission by static mechanism. Molecular docking revealed that the secalin peptides interacted with ADAM17 via zinc cofactor coordination, hydrogen bonds, and hydrophobic interactions. These findings demonstrate that food-derived zinc-chelating peptides are potential anti-inflammatory therapeutic agents.