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Towards Celiac-safe foods : Decreasing the affinity of transglutaminase 2 for gliadin by addition of ascorbyl palmitate and ZnCl2 as detoxifiers

Engstrom, N. LU ; Saenz-Méndez, P. ; Scheers, J. and Scheers, N. (2017) In Scientific Reports 7(1).
Abstract

Initiation of celiac disease is triggered in the gastrointestinal tract by transglutaminase 2 (TG2) assisted deamidation of gluten peptides. Deamidation is a side-reaction to transamidation and occurs if primary amines are absent. In contrast to deamidation, transamidation does not trigger an immune response. The aim of the study was to identify a suitable food additive that interacts with TG2 binding motives in gluten-derived peptides to prevent deamidation/transamidation. Homology modelling of ±2-gliadin and computational screening of compounds for their binding affinity to a common TG2 binding motive (P)QLP were done by using computational approaches followed by experimental testing of TG2 activity. A database containing 1174... (More)

Initiation of celiac disease is triggered in the gastrointestinal tract by transglutaminase 2 (TG2) assisted deamidation of gluten peptides. Deamidation is a side-reaction to transamidation and occurs if primary amines are absent. In contrast to deamidation, transamidation does not trigger an immune response. The aim of the study was to identify a suitable food additive that interacts with TG2 binding motives in gluten-derived peptides to prevent deamidation/transamidation. Homology modelling of ±2-gliadin and computational screening of compounds for their binding affinity to a common TG2 binding motive (P)QLP were done by using computational approaches followed by experimental testing of TG2 activity. A database containing 1174 potential food grade ligands was screened against the model of ±2-gliadin (27 out of 33 aa). Out of the five best ligands, ascorbyl palmitate, was observed to decrease TG2 transamidation of gliadin by 82% ± 2%. To completely silence the transamidation, we added zinc chloride (ZnCl2), and thereby reached a 99% ± 1% inhibition of TG2 activity. In addition, we conducted a pilot experiment in which ascorbyl palmitate was observed to decrease TG2 deamidation of gliadin completely. We propose ascorbyl palmitate in combination with ZnCl2 with the future perspective to become an additive in celiac-safe foods.

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author
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publishing date
type
Contribution to journal
publication status
published
subject
in
Scientific Reports
volume
7
issue
1
article number
77
publisher
Nature Publishing Group
external identifiers
  • scopus:85038832774
  • pmid:28250436
ISSN
2045-2322
DOI
10.1038/s41598-017-00174-z
language
English
LU publication?
no
id
e48edcf9-7da9-4df2-80db-7fca8a7ad214
date added to LUP
2020-11-17 14:24:41
date last changed
2024-10-03 12:52:38
@article{e48edcf9-7da9-4df2-80db-7fca8a7ad214,
  abstract     = {{<p>Initiation of celiac disease is triggered in the gastrointestinal tract by transglutaminase 2 (TG2) assisted deamidation of gluten peptides. Deamidation is a side-reaction to transamidation and occurs if primary amines are absent. In contrast to deamidation, transamidation does not trigger an immune response. The aim of the study was to identify a suitable food additive that interacts with TG2 binding motives in gluten-derived peptides to prevent deamidation/transamidation. Homology modelling of ±2-gliadin and computational screening of compounds for their binding affinity to a common TG2 binding motive (P)QLP were done by using computational approaches followed by experimental testing of TG2 activity. A database containing 1174 potential food grade ligands was screened against the model of ±2-gliadin (27 out of 33 aa). Out of the five best ligands, ascorbyl palmitate, was observed to decrease TG2 transamidation of gliadin by 82% ± 2%. To completely silence the transamidation, we added zinc chloride (ZnCl<sub>2</sub>), and thereby reached a 99% ± 1% inhibition of TG2 activity. In addition, we conducted a pilot experiment in which ascorbyl palmitate was observed to decrease TG2 deamidation of gliadin completely. We propose ascorbyl palmitate in combination with ZnCl<sub>2</sub> with the future perspective to become an additive in celiac-safe foods.</p>}},
  author       = {{Engstrom, N. and Saenz-Méndez, P. and Scheers, J. and Scheers, N.}},
  issn         = {{2045-2322}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Scientific Reports}},
  title        = {{Towards Celiac-safe foods : Decreasing the affinity of transglutaminase 2 for gliadin by addition of ascorbyl palmitate and ZnCl2 as detoxifiers}},
  url          = {{http://dx.doi.org/10.1038/s41598-017-00174-z}},
  doi          = {{10.1038/s41598-017-00174-z}},
  volume       = {{7}},
  year         = {{2017}},
}