Cyclization: A potential effective modification strategy for umami peptides.

Cyclization enhances various properties of peptides and has been widely used in life sciences, but it has not been explored in taste peptides. Our study found that cyclization of the N/C termini of the peptides (head-to-tail) via amide bond is a potentially effective modification strategy for umami peptides to improve their properties. This is the first report on umami cyclic peptides. Umami peptides were downloaded from TastePeptidesDB and linear/cyclic structures were generated for docking with umami receptors, of which 138 groups completed docking. The lower-scoring group was chosen for contact matrix analysis, yielding three representative umami peptides after dimensionality reduction and clustering. Sensory evaluation of the three groups (chemically synthesized linear and cyclic peptides) revealed that the umami intensity of DPLRGGY was significantly increased after cyclization, with recognition threshold dropped from 0.186 to 0.051 mM; while the umami intensity of RGEPNND decreased. Applying molecular fingerprints and descriptors analysis, it was found that polarity and threshold differences were correlated (|Corr| ≥0.5). DFT calculations were applied to analyze the electron cloud structure and found that electrostatic rearrangement was the main reason for the difference in umami intensity after cyclization. This study proposed a potential cyclization strategy for the development of novel umami peptides and explained the essential reasons for the cyclization effect, providing a new strategy for further expanding the application to explore more efficient umami peptide structural derivatives.