Study of abberant modifications in peptides as a test bench to investigate the immunological response to non-enzymatic glycation

Title:

Study of abberant modifications in peptides as a test bench to investigate the immunological response to non-enzymatic glycation

Creator:

Nuti, F., Gallo, A., Real-Fernandez, F., Rentier, C., Rossi, G., Piarulli, F., Traldi, P., Carganico, S., Rovero, P., Lapolla, A., and Papini, A. M.

Identifier:

https://cdk.lib.cas.cz/client/handle/uuid:7dc493c2-25aa-4ae1-8cf7-9ecaa5e46de5
uuid:7dc493c2-25aa-4ae1-8cf7-9ecaa5e46de5

Subject:

protein glycation, immunological response, peptide, β-turn peptide structure, type 1 diabetes, and SP-ELISA

Type:

model:article and TEXT

Format:

bez média and svazek

Description:

A side effect of diabetes is formation of glycated proteins and, from them, production of advanced early glycation end products that could determine aberrant immune responses at the systemic level. We investigated a relevant aberrant post-translational modification (PTM) in diabetes based on synthetic peptides modified on the lysine side chain residues with 1-deoxyfructopyranosyl moiety as a possible modification related to glycation. The PTM peptides were used as molecular probes for detection of possible specific autoantibodies developed by diabetic patients. The PDC-E2(167-186) sequence from the pyruvate dehydrogenase complex was selected and tested as a candidate peptide for antibody detection. The structure-based designed type I’ β-turn CSF114 peptide was also used as a synthetic scaffold. Twenty-seven consecutive type 1 diabetic patients and 29 healthy controls were recruited for the study. In principle, the ‘chemical reverse approach’, based on the use of patient sera to screen the synthetic modified peptides, leads to the identification of specific probes able to characterize highly specific autoantibodies as disease biomarkers of autoimmune disorders. Quite surprisingly, both peptides modified with the (1-deoxyfructosyl)-lysine did not lead to significant results. Both IgG and IgM differences between the two populations were not significant. These data can be rationalized considering that i) IgGs in diabetic subjects exhibit a high degree of glycation, leading to decreased functionality; ii) IgGs in diabetic subjects exhibit a privileged response vs proteins containing advanced glycation products (e.g., methylglyoxal, glyoxal, glucosone, hydroimidazolone, dihydroxyimidazolidine) and only a minor one with respect to (1-deoxyfructosyl)-lysine. and Corresponding authors: Anna Maria Papini; Annunziata Lapolla

Language:

English

Rights:

http://creativecommons.org/publicdomain/mark/1.0/
policy:public

Coverage:

[195]-202

Source:

Folia biologica | 2019 Volume:65 | Number:4

Harvested from:

CDK

Metadata only:

false