Enzymatic degradation of endomorphins

Janecka, Anna; Staniszewska, Renata; Gach, Katarzyna; Fichna, Jakub

doi:10.1016/j.peptides.2008.07.015

Cited by 72 publications

(47 citation statements)

References 60 publications

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“…2 However, peripheral administration of EMs meets with failure due to their inability to penetrate the blood−brain barrier (BBB) 3 and to their rapid degradation by peptidases. 4 Numerous chemical modifications have been developed to increase stability and bioavailability of EM analogues. 5,6 So far, only a few have been reported to be able to gain access to the central nervous system (CNS) and produce analgesia after peripheral administration.…”

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confidence: 99%

Synthesis of Mixed Opioid Affinity Cyclic Endomorphin-2 Analogues with Fluorinated Phenylalanines

Piekielna

Perlikowska

do-Rego

et al. 2015

ACS Med. Chem. Lett.

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As part of our continuing studies on the structure−activity relationships of cyclic pentapeptides based on the structure of endomorphin-2 (EM-2), we report here the synthesis and biological activities of a new series of analogues of a general sequence Tyr/Dmt-c[D-Lys-Phe-Phe-Asp]NH 2 (where Dmt = 2′,6′-dimethyltyrosine), incorporating fluorinated amino acids: 4-fluorophenylalanine (4-F-Phe), 2,4-difluorophenylalanine (2,4-F-Phe), or 4-trifluoromethylphenylalanine (4-CF 3 -Phe) instead of the Phe residue in position 3 or 4. Depending on the fluorinated amino acid residue and its position in the sequence, analogues were mixed, high affinity MOP/KOP receptor agonists, MOP/DOP/KOP agonists, or selective KOP agonists. The in vitro potencies and efficacies of all novel analogues were assessed in calcium mobilization assay. The most potent analogues, Dmt-c[D-Lys-Phe-4-F-Phe-Asp]NH 2 and Dmt-c[D-Lys-Phe-2,4-F-Phe-Asp]NH 2 , were tested in vivo in the mouse hot-plate test. They produced strong antinociceptive effect not only after intracerebroventricular but also after intraperitoneal injection, indicating that they were able to cross the blood−brain barrier.

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confidence: 99%

Synthesis of Mixed Opioid Affinity Cyclic Endomorphin-2 Analogues with Fluorinated Phenylalanines

Piekielna

Perlikowska

do-Rego

et al. 2015

ACS Med. Chem. Lett.

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“…If these peptides cross the blood-brain barrier and reach the CNS (in large amounts), brain function may be altered. 51 However, there are several pieces of evidence against this theory, such as the low affinity of exorphins for opioid receptors, the presence of dietetic gluten/caseinderived peptides with antagonistic activity on opioid receptors and the failure to demonstrate abnormally high concentrations of opioid peptides in either the plasma or the nervous system of patients with an ASD. 52 A recent systematic review concluded that the evidence to support a gluten-free, casein-free diet is limited and weak, considering that dietary restrictions might be responsible for further social withdrawal and integration, in addition to potential adverse clinical effects.…”

Section: Specific Treatments For Asdsmentioning

confidence: 99%

Autism spectrum disorders and intestinal microbiota

et al. 2015

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“…After digestion, certain types of proteins could cross the intestinal mucosa intact 14 , if this were more permeable than normal, this being the case when it is impaired by immunological factors or by lesions in the case of celiac disease. If these peptides, transported by the blood stream, were to cross the blood-brain barrier and reach the central nervous system in large quantities it would affect brain functioning 15 . The hydrolysis of proteins from cereals and milk would generate exogenous neuropeptides (exorphines) such as gluteomorphins from gluten and betacasomorphins from casein.…”

Section: Opioid Theory For Autism Spectrum Disordersmentioning

confidence: 99%

Evidence of the Gluten-Free and Casein-Free Diet in Autism Spectrum Disorders

et al. 2014

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In autism spectrum disorders, many parents resort to alternative treatments and these are generally perceived as risk free. Among these, the most commonly used is the gluten-free casein-free diet. The objective of this work was to conduct a systematic review of studies published from 1970 to date related to the gluten-free casein-free diet in autism spectrum disorders patients. Few studies can be regarded as providing sound scientific evidence since they were blinded randomised controlled trials, and even these were based on small sample sizes, reducing their validity. We observed that the evidence on this topic is currently limited and weak. We recommend that it should be only used after the diagnosis of an intolerance or allergy to foods containing the allergens excluded in gluten-free casein-free diets. Future research should be based on this type of design, but with larger sample sizes.

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Enzymatic degradation of endomorphins

Cited by 72 publications

References 60 publications

Synthesis of Mixed Opioid Affinity Cyclic Endomorphin-2 Analogues with Fluorinated Phenylalanines

Synthesis of Mixed Opioid Affinity Cyclic Endomorphin-2 Analogues with Fluorinated Phenylalanines

Autism spectrum disorders and intestinal microbiota

Evidence of the Gluten-Free and Casein-Free Diet in Autism Spectrum Disorders

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