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Does glycation really distort the peptide α-helicity?

Mariño, Laura, Casasnovas, Rodrigo, Ramis, Rafael, Vilanova, Bartolomé, Ortega-Castro, Joaquín, Frau, Juan, Adrover, Miquel
International journal of biological macromolecules 2019 v.129 pp. 254-266
glycation, lysine, models, pH, post-translational modification, protein structure, proteins, ribose, schiff bases
The understanding of the effect of non-enzymatic post-translational modifications on the protein structure is essential to unveil the molecular mechanisms underlying their related pathological processes. Among those modifications, protein glycation emerges as one of the main responsible for the development of diabetes-related diseases. While some reports suggest that glycation has a chaotropic effect, others indicate that it does not modify the protein structure. Here we aim to better clarify this effect and therefore, we have studied the effect of glycation mediated by ribose and methylglyoxal on a fifteen-residue model peptide, which readily undergoes a pH-induced coil-helix transition. Neither ribose nor methylglyoxal were able to induce the structuration of the peptide at physiological pH. Moreover, neither ribose nor methylglyoxal severely modified the α-helical structure acquired by the peptide at pH ~ 3. Among the different glycation products experimentally detected (i.e. the ribose-derived Schiff base; the Amadori compound; Nε-(carboxyethyl)lysine; Nε-(carboxymethyl)lysine; and MOLD), the Amadori compound was the one with the greatest impact on the α-helicity. Our data contribute to clarify the effect of glycation on the structure of proteins by proving that the glycation products do not necessarily affect the α-helical structure of a peptide stretch.