Molecular characterization of sequence-driven peptide glycation

Peptide glycation is an important, yet poorly understood reaction not only found in food but also in biological systems. The enormous heterogeneity of peptides and the complexity of glycation reactions impeded large-scale analysis of peptide derived glycation products and to understand both the contributing factors and how this affects the biological activity of peptides. Analyzing time-resolved Amadori product formation, we here explored site-specific glycation for 264 peptides. Intensity profiling together with in-depth computational sequence deconvolution resolved differences in peptide glycation based on microheterogeneity and revealed particularly reactive peptide collectives. These peptides feature potentially important sequence patterns that appear in several established bio- and sensory-active peptides from independent sources, which suggests that our approach serves system-wide applicability.


Fig:  Analysis of tryptone glucose model systems by UHPLC-QTOF-MS. (a)Experimental design—high-resolution mass spectrometry was used to analyze tryptone glucose model systems and for the identification of site-specific non-enzymatic glycation. (a) The bar plot illustrates the number of peptides provided by an in silico tryptic casein digest (72) compared to tryptone (264). (b) A bar plot shows the number of C-terminal amino acids observed for tryptone peptides (light blue) and a theoretical casein digest by trypsin (dark blue). Tryptic digestion predominantly forms peptides with C-terminal lysine or arginine. (c) A casein protein heatmap represents how often (relative scale) detected tryptone peptides covered the same amino acid sequence in the proteins, showing which protein substructures contribute to peptide heterogeneity of the model systems. Dipeptides were removed for more sequence specificity.

We generated a pattern peptide map and propose that in peptide glycation the herein identified molecular checkpoints can be used as indication of sequence reactivity.

Berger, M.T., Hemmler, D., Walker, A. et al. Molecular characterization of sequence-driven peptide glycation. Sci Rep 11, 13294 (2021).

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