Ex vivo screening of prospective peptide drugs: New approaches

Андреева, Л. А.; Mezentseva, M. V.; Nagaev, I. Yu.; Shapoval, I. M.; Щербенко, В. Э.; Potapova, Lyudmila Aleksandrovna; Russu, L. I.; Narovlyansky, Alexander N.; Ершов, Ф. И.; Myasoedov, N. F.

doi:10.1134/s0012496610050029

Cited by 6 publications

(5 citation statements)

References 5 publications

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“…On the one hand, the protective effect of glyprolines on various inflammation-related disorders was conclusively established. Thus, they not only have a protective effect on the gastric mucosa during the formation of ulcers, but also protect cells from oxidative stress and are involved in the regulation of the immune status of the organism [10]. …”

Section: Resultsmentioning

confidence: 99%

Prolyl-glycyl-proline (PGP) Peptide Prevents an Increase in Vascular Permeability in Inflammation

et al. 2017

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This study was aimed at investigating the effect of prolyl-glycyl-proline (PGP) tripeptide on vascular permeability in rats with an inflammation. It was found that the peptide reduces the rat paw edema induced by a subcutaneous administration of histamine to the same extent as the conventional anti-inflammatory agent diclofenac. However, an assessment of the relative expression level of the cox-2 gene at the inflammation focus using real-time PCR showed that, in contrast to diclofenac, PGP does not affect the cox-2 gene expression. This is indicative of the fact that they have different mechanisms of action. We used the model of acute peritonitis induced by an intraperitoneal injection of thioglycolate to demonstrate that the inflammatory response of an organism is accompanied by increased vascular permeability in the tissues of the stomach and small intestine. Pre-administration (30 minutes before the induction of the inflammation) of PGP prevented this increase, whereby the level of vascular permeability, exudate volume in the peritoneal cavity, and the amount of the Evans Blue dye in this exudate remained at the control level. Therefore, these results suggest that the anti-inflammatory action of PGP is based on its ability to prevent an increase in vascular permeability.

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Section: Resultsmentioning

confidence: 99%

Prolyl-glycyl-proline (PGP) Peptide Prevents an Increase in Vascular Permeability in Inflammation

et al. 2017

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“…The introduction of Selank in vivo induced the expression of the Ifnα gene, without affecting the expression of the Il4, Il10, and Tnfα genes. The mechanism underlying the antiviral action of Selank is probably linked to its ability to modulate the balance of the Th1/Th2 cytokines [178,179].…”

Section: Immunomodulatory Effectmentioning

confidence: 99%

“…Together with its anxiolytic and nootropic actions, Selank elicits a pronounced immunomodulatory activity [179,180]. Previously, it was shown that Selank administration to the rat brain leads to changes in the levels of the Cx3cr1 mRNA, which encodes a chemokine receptor involved in the promotion of the immune response.…”

Section: Effect Of Selank On the Transcriptomementioning

confidence: 99%

A New Generation of Drugs: Synthetic Peptides Based on Natural Regulatory Peptides

Kolomin¹,

Шадрина²,

Slominsky³

et al. 2013

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Natural regulatory peptides are biologically active compounds that are produced by various cells and provide a link among the main regulatory systems of the body. The field of research into the biologic activity of endogenous regulatory peptides is extremely vast. These peptides affect the cardiovascular, immune, reproductive, endocrine, digestive, and other systems, alter energy metabolism, and are especially effective in the regulation of the central nervous system. Despite of the wide range of preventive and therapeutic effects of natural regulatory peptides and proteins, their application in clinical practice is difficult. This is primarily because of their extreme instability, as they are rapidly degraded by proteases of the gastrointestinal tract, blood, cerebrospinal fluid, and other biologic media. Compounds with higher stability (i.e., a considerably longer half-life compared with that of natural molecules) and the ability to provide a directional effect on the various body systems were obtained from modifications of endogenous regulatory peptides. Synthetic analogs of regulatory peptides, as a rule, contain only natural amino acids in their composition, and their biodegradation does not lead to the formation of toxic products; thus, they have fewer side effects. This review focuses on the consideration of two synthetic regulatory peptides, Semax and Selank, which were the bases for the creation of new drugs that are used effectively in the treatment of various diseases of the nervous system. The synthetic analog of an adrenocorticotropic hormone 4-10 fragment (ACTH 4-10) Semax is a powerful neuroprotective agent that is particularly effective as a therapy for stroke. Selank was synthesized on the basis of the natural immunomodulator tuftsin. Selank is a powerful anxiolytic that is used as a therapy for generalized anxiety disorder and neurasthenia without sedative and muscle-relaxant effects. This review presents the results of research aimed at studying the influence of these peptides on the transcriptome of brain cells. The problems of drugs developed based on the clinical activities of Semax and Selank are discussed separately.

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“…Of particular interest today are drugs from the group of peptide analogues with proven regulatory https://doi.org/10.35630/2199-885X/2019/9/3.9 function relative to homeostasis and the ability to participate in the formation of adaptive changes under the influence of stress factors [11]. It was established that peptide compounds related to glyprolins, along with the above properties, have neuroprotective, neurotrophic, anxiolytic and other types of activity, however, information on the immunotropic effect of these substances is insufficient [12,13].…”

Section: Introductionmentioning

confidence: 99%

The influence of pro-gly-pro-leu on the level of cytokines under the conditions of "social" stress

Самотруева¹,

Ясенявская²,

Цибизова³

et al. 2019

AREM

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The experiment investigated the effect of Pro-Gly-Pro-Leu on the level of cytokines under the conditions of "social" stress. The level of cytokines under study was determined by enzyme-linked immunosorbent assay. The stress-induced changes observed in the experiment consist in increasing the production of IL-1β, IL-6, TNF-α and TGF-β, which allows us to consider stress exposure as an inducer of the production of pro-inflammatory interleukins and various growth factors. It was found that the introduction of Pro-Gly-Pro-Leu is accompanied by the restoration of increased values of the studied cytokines in stressed animals almost to the level of indicators of the control group. The obtained results indicate the pronounced stress-protective properties of this compound, which are manifested in the restoration of the level of the studied cytokines to the level of control values. K E Y w O R D S-"social" stress, peptide, glyprolins, cytokines, interleukin-1β, interleukin-4, interleukin-6, tumor necrosis factor-α, transforming growth factor β1.

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Ex vivo screening of prospective peptide drugs: New approaches

Cited by 6 publications

References 5 publications

Prolyl-glycyl-proline (PGP) Peptide Prevents an Increase in Vascular Permeability in Inflammation

Prolyl-glycyl-proline (PGP) Peptide Prevents an Increase in Vascular Permeability in Inflammation

A New Generation of Drugs: Synthetic Peptides Based on Natural Regulatory Peptides

The influence of pro-gly-pro-leu on the level of cytokines under the conditions of "social" stress

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