Analgesic activity of dipeptide Tyr-Pro

Guzevatykh, L. S.; Воронина, Т. А.; Emel'yanova, T. G.; Андреева, Л. А.; Alfeeva, L. Yu.; Seredenin, S. B.; Myasoedov, N. F.

doi:10.1134/s1062359008010081

Cited by 9 publications

(4 citation statements)

References 27 publications

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“…Tyr-pro is the minimal length peptide which has been shown by two laboratories to possess opioid activity. 23,24 Tyr-pro can form a hydrogen bonded virtual ring and peptide turn which is consistent with this proposition (Fig. 19).…”

Section: Amino Acids With the L Conformation Are Exclusivesupporting

confidence: 84%

Stereochemical Basis for a Unified Structure Activity Theory of Aromatic and Heterocyclic Rings in Selected Opioids and Opioid Peptides

Goldberg

2010

Perspect Medicin Chem

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This paper presents a novel unified theory of the structure activity relationship of opioids and opioid peptides. It is hypothesized that a virtual or known heterocyclic ring exists in all opioids which have activity in humans, and this ring occupies relative to the aromatic ring of the drug, approximately the same plane in space as the piperidine ring of morphine. Since the rings of morphine are rigid, and the aromatic and piperidine rings are critical structural components for morphine’s analgesic properties, the rigid morphine molecule allows for approximations of the aromatic and heterocyclic relationships in subsequent drug models where bond rotations are common. This hypothesis and five propositions are supported by stereochemistry and experimental observations.Proposition #1 The structure of morphine provides a template. Proposition #2 Steric hindrance of some centric portion of the piperidine ring explains antagonist properties of naloxone, naltrexone and alvimopam. Proposition #3 Methadone has an active conformation which contains a virtual heterocyclic ring which explains its analgesic activity and racemic properties. Proposition #4 The piperidine ring of fentanyl can assume the morphine position under conditions of nitrogen inversion. Proposition #5 The first 3 amino acid sequences of beta endorphin (l-try-gly-gly) and the active opioid dipeptide, l-tyr-pro, (as a result of a peptide turn and zwitterion bonding) form a virtual piperazine-like ring which is similar in size, shape and location to the heterocyclic rings of morphine, meperidine, and methadone. Potential flaws in this theory are discussed.This theory could be important for future analgesic drug design.

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Section: Amino Acids With the L Conformation Are Exclusivesupporting

confidence: 84%

Stereochemical Basis for a Unified Structure Activity Theory of Aromatic and Heterocyclic Rings in Selected Opioids and Opioid Peptides

Goldberg

2010

Perspect Medicin Chem

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“…There is experimental evidence that the two dipeptides, tyr-pro and tyr-gly can produce dose related analgesia that is reversed by naloxone. 27,28 The structure of tyr-pro and try-gly could assume an active conformation of an aromatic and virtual hetereocylic (piperazine like) ring which in theory may be related to analgesia. 16 Ethanol, cholesterol and 3-glucose are possible conjugates which can be used to form the lead OPE.…”

Section: Identifying Lead Compoundsmentioning

confidence: 99%

Low Molecular Weight Opioid Peptide Esters Could be Developed as a New Class of Analgesics

Goldberg

2011

Perspect Medicin Chem

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Low molecular weight opioid peptide esters (OPE) could become a class of analgesics with different side effect profiles than current opiates. OPE may have sufficient plasma stability to cross the blood brain barrier (BBB), undergo ester hydrolysis and produce analgesia. OPE of dipeptides, tyr-pro and tyr-gly conjugated to ethanol have a structure similar to the anesthestic agent, etomidate. Based upon the analgesic activity of dipeptide opioids, Lipinski’s criteria, and permeability of select GABA esters to cross the BBB, opioid peptides (OP) conjugated to ethanol, cholesterol or 3-glucose are lead recommendations. Preliminary animal data suggests that tyr-pro-ethyl ester crosses the BBB and unexpectedly produces hyperalgesia. Currently, there are no approved OP analgesics available for clinical use. Clinical trials of good manufacturing practice OP administered to patients suffering from chronic pain with indwelling intrathecal pumps could resolve the issue that OP may be superior to opiates and may redirect research.

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“…It was reported that the fermented meat sauce possessed extremely high antioxidant activity against the hydroxyl radical (>90%) that may due to the presence of the low‐molecular‐weight tripeptide, QYP (406.26 g/mol), and two other unidentified substances with molecular weights of 375.30 and 230.20 g/mol, respectively. The sequence YP presented in the peptide was deduced to be the reason for the peptide's high antioxidant activity as it has been reported to have association with analgesic effect, enhancement of memory retention, and ACE‐I properties (Guzevatykh et al., 2008; Ohata et al., 2016).…”

Section: Sourcesmentioning

confidence: 99%

Bioactive peptides from food fermentation: A comprehensive review of their sources, bioactivities, applications, and future development

Chai

Voo

Chen

2020

Comp Rev Food Sci Food Safe

146

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Bioactive peptides (BPs) are specific protein fragments that exert various beneficial effects on human bodies and ultimately influence health, depending on their structural properties and amino acid composition and sequences. By offering promising solutions to solve diverse health issues, the production, characterization, and applications of food-derived BPs have drawn great interest in the current literature and are of particular interest to the food and pharmaceutical industries. The microbial fermentation of protein from various sources is indubitably a novel way to produce BPs with numerous beneficial health effects. Apart from its lower cost as compared to enzymes, the BPs produced from microbial fermentation can be purified without further hydrolysis. Despite these features, current literature shows dearth of information on the BPs produced from food via microbial fermentation. Hence, there is a strong necessity to explore the BPs obtained from food fermentation for the development of commercial nutraceuticals and functional foods. As such, this review focuses on the production of BPs from different food sources, including the extensively studied milk and milk products, with emphasis on microbial fermentation. The structure-activity (antihypertensive, antioxidant, antimicrobial, opiate-like, anti-inflammatory, anticancer/antiproliferative, antithrombotic, hypolipidemic, hypocholesterolemic, and mineral binding) relationship, potential applications, future development, and challenges of BPs obtained from food fermentation are also discussed.

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Analgesic activity of dipeptide Tyr-Pro

Cited by 9 publications

References 27 publications

Stereochemical Basis for a Unified Structure Activity Theory of Aromatic and Heterocyclic Rings in Selected Opioids and Opioid Peptides

Stereochemical Basis for a Unified Structure Activity Theory of Aromatic and Heterocyclic Rings in Selected Opioids and Opioid Peptides

Low Molecular Weight Opioid Peptide Esters Could be Developed as a New Class of Analgesics

Bioactive peptides from food fermentation: A comprehensive review of their sources, bioactivities, applications, and future development

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