1. Opioid peptides derived from food proteins suppress aggregation and promote reactivation of partly unfolded stressed proteins
Z M Bumagina,A S Kasakov,B Ya Gurvits,V V Shubin,N V Artemova Peptides . 2010 Feb;31(2):332-8. doi: 10.1016/j.peptides.2009.11.025.
A new view of the opioid peptides is presented. The potential of small peptides derived from precursor food proteins, to bind to partly unfolded stressed proteins to prevent their irreversible aggregation and inactivation has been demonstrated in various in vitro test systems: dithiothreitol-induced aggregation of alpha-lactalbumin (LA), heat-induced aggregation of alcohol dehydrogenase (ADH), and aggregation and inactivation of bovine erythrocyte carbonic anhydrase (CA) in the process of its refolding after removal of stress conditions. Using dynamic light scattering (DLS), turbidimetry, fluorescence, and circular dichroism measurements protective effects of the synthetic opioid peptides: exorphin C from wheat gluten (Tyr-Pro-Ile-Ser-Leu), rubiscolin-5 from spinach ribulose-bisphosphate-carboxylase/oxygenase (Rubisco) (Tyr-Pro-Leu-Asp-Leu), and hemorphin-6 from bovine hemoglobin (Tyr-Pro-Trp-Thr-Gln-Arg) have been revealed. We have demonstrated the concentration-dependent suppression of light scattering intensity of aggregates of LA and ADH in the presence of the peptides, the population of nanoparticles with higher hydrodynamic radii being shifted to the lower ones, accompanied by an increase in the lag period of aggregation. The presence of the peptides in the refolding solution was shown to assist reactivation of CA and enhance the yield of the CA soluble protein. The results suggest that bioactive food protein fragments may be regarded as exogenous supplements to the endogenous defense mechanisms of the human organism under stress conditions.
2. Genetic predictors of celiac disease, lactose intolerance, and vitamin D function and presence of peptide morphins in urine of children with neurodevelopmental disorders
Vladimir Gašić,Nikola Kotur,Branka Zukić,Sonja Pavlović,Biljana Stanković,Katarina Bojović,Đurđica Ignjatović,Dijana Krstić-Milošević Nutr Neurosci . 2019 Jan;22(1):40-50. doi: 10.1080/1028415X.2017.1352121.
Gastrointestinal disturbances, nutritional deficiencies, and food intolerances are frequently observed in children with neurodevelopmental disorders (NDD). To reveal possible association of celiac disease risk variants (HLA-DQ), lactose intolerance associated variant (LCT-13910C>T) as well as variant associated with vitamin D function (VDR FokI) with NDD, polymerase chain reaction-based methodology was used. Additionally, intestinal peptide permeability was estimated in NDD patients and healthy children by measuring the level of peptides in urine using high-performance liquid chromatography. Levels of opioid peptides, casomorphin 8, and gluten exorphin C were significantly elevated in urine samples of NDD patients (P = 0.004 and P = 0.005, respectively), but no association of genetic risk variants for celiac disease and lactose intolerance with NDD was found. Our results indicate that increased intestinal peptide permeability observed in analyzed NDD patients is not associated with genetic predictors of celiac disease or lactose intolerance. We have also found that FF genotype of VDR FokI and lower serum levels of vitamin D (25-OH) showed association with childhood autism (CHA), a subgroup of NDD. We hypothesize that vitamin D might be important for the development of CHA.
3. Gluten exorphin C. A novel opioid peptide derived from wheat gluten
S Fukudome,M Yoshikawa FEBS Lett . 1993 Jan 18;316(1):17-9. doi: 10.1016/0014-5793(93)81727-h.
A novel opioid peptide, Tyr-Pro-Ile-Ser-Leu, was isolated from the pepsin-trypsin-chymotrypsin digest of wheat gluten. Its IC50 values were 40 microM and 13.5 microM in the GPI and MVD assays, respectively. This peptide was named gluten exorphin C. Gluten exorphin C had a structure quite different from any of the endogenous and exogenous opioid peptides ever reported in that the N terminal Tyr was the only aromatic amino acid. The analogs containing Tyr-Pro-X-Ser-Leu were synthesized to study its structure-activity relationship. Peptides in which X was an aromatic amino acid or an aliphatic hydrophobic amino acid had opioid activity.
