Pea protein-derived peptides as antagonists of T2R4, T2R7, and T2R14 human bitter taste receptors

Rising concerns over excessive sugar intake and its health risks drive the need for sustainable alternatives. Food protein-derived peptides offer a potential bioactive approach, reducing sugar dependency by modulating taste perception through bitter taste receptor (T2R) antagonism. This study determined the bitter taste-masking potential of pea protein hydrolysate (PPH), using human sensory panel, electronic tongue analysis, and cell-based assays to assess the inhibition of bitter taste receptors (T2Rs). Taste panel evaluation showed that the PPH at 10 mg/mL significantly (p<0.05) reduced bitterness intensity of a quinine solution from an unacceptable level to acceptable. RP-HPLC fractionation of the PPH revealed two hydrophilic fractions that significantly inhibited quinine and diphenhydramine induced calcium mobilization in HEK293T cells expressing T2R4, T2R7, and T2R14, confirming receptor-specific antagonism. LC-MS/MS analysis identified six key peptides (SSGVD, KKPPASAAP, AAPAGHG, GHPDNGNC, KKSLL, and DDPD) among which GHPDNGNC, SSGVD and KKSLL showed potent antagonistic activity against quinine and diphenhydramine activation of T2R14 . Electronic tongue analysis showed that KKSLL, GHPDNGNC, and SSGVD exhibited 100% suppression of quinine bitterness while they reduced diphenhydramine bitterness by 78.8%, 73.1%, and 69.1%, respectively. These peptides also inhibited angiotensin-converting enzyme activity, with SSGVD showing the strongest effect (IC₅₀ = 138.46 ± 5.21 µM). Taken together, pea protein-derived peptides represent multifunctional agents that can modulate bitterness perception while providing additional health benefits such as potential antihypertensive effects, supporting applications in developing functional, low-sugar, and sustainable food systems.