Stability of His-Phe-Arg-Trp-Pro-Gly-Pro to Leucine Aminopeptidase, Carboxypeptidase Y, and Rat Nasal Mucus, Blood, and Plasma

Шевченко, К. В.; Dulov, S. A.; Andreeva, L. A.; Nagaev, I. Yu.; Шевченко, В. П.; Radilov, A. S.; Myasoedov, N. F.

doi:10.1134/s1068162016020126

Cited by 6 publications

(8 citation statements)

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“…Qualitative (component) and quantitative of peptide fragments (products of the initial peptide biodegradation) depends much on even a single amino acid modification in the structure of a native peptide . Because of the specific proteolysis of peptide molecules, which also depends on their physiological liquid or tissue milieu, biosynthesis of a singular group of the new short peptides (fragments of the initial molecules, which in turn are able to show unique physiological activity of their own) can proceed in the body. The effect of the totality of the generated peptides, which we earlier termed the synacton (biologically active putative products of N‐ and C‐terminal proteolysis of the initial peptide), must be assessed in the investigation of the mechanism of action of individual regulatory molecules.…”

Section: Introductionmentioning

confidence: 99%

Synacton and individual activity of synthetic and natural corticotropins

V’yunova

Andreeva

Шевченко

et al. 2016

J of Molecular Recognition

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Short endogenous peptides represent one of the most important constituents of the mammalian body's general regulatory system. Some synthesized analogs and modified natural peptides (eg, corticotropins) also show high biological activity. Nevertheless, the mechanism of action of regulatory peptides remains unclear. To explain the effects of peptides of intermolecular processes, the hypothesis that a synactonal mechanism underlies the action of regulatory peptides, exemplified by the heptapeptide Semax, has been proposed. Thus, in the total pool of Semax metabolites, which includes the cleavage products of the parental molecule, we can distinguish the functional core, represented by the major metabolic products-peptides HFPGP and PGP. These peptides have their own binding sites with similar although differing characteristics. Together with Semax, they constitute a single complex of bioregulators acting in a certain sequence and in interaction, ie, synacton. It can be assumed that the diverse clinically significant effects of the drug Semax are determined by its synacton. Specific interactions between some tritium-labeled peptides (basic constituents of the Semax synacton) and plasma membranes of neurons have been characterized. Only a few peptides of the Semax synacton showed competitive activity for the Semax binding sites. Fragments comprising 5 amino acid residues (EHFPG and HFPGP) showed the highest competitive activity. We also characterized the processes of specific ligand-receptor interactions of some tritium-labeled corticotropins ([ H-Pro]MEHFPGP, [ H-Pro]HFPGP, and [ H-Pro]PGP) by applying mathematical discriminative models (Scatchard, Hill, Bjerrum, and Lineweaver-Burk plots). So the intermolecular interactions of these peptides with plasma membranes of neuronal brain targets are probably not limited by specific binding at orthosteric sites. The effect of peptides that act in the synacton considerably extends the regulatory potential of the initial molecule.

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Section: Introductionmentioning

confidence: 99%

Synacton and individual activity of synthetic and natural corticotropins

V’yunova

Andreeva

Шевченко

et al. 2016

J of Molecular Recognition

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“…The MC family includes ACTH and MSH (α-, β-and γ-MSH), as well as fragments of these hormones and their synthetic analogs. The common sequence for all MC is ACTH (6)(7)(8)(9) or FRWG, which is necessary for binding to all known types of MC receptors [2]. Of particular interest is the ability of ACTH and MSH, as well as their fragments lacking hormonal activity, to accelerate the training of animals and improve the preservation of skills.…”

Section: Introductionmentioning

confidence: 99%

“…Of particular interest is the ability of ACTH and MSH, as well as their fragments lacking hormonal activity, to accelerate the training of animals and improve the preservation of skills. The most active of the studied peptides is ACTH (4)(5)(6)(7)(8)(9)(10). The smallest ACTH fragment retaining nootropic activity is ACTH(4-7).…”

Section: Introductionmentioning

confidence: 99%

“…However, it was also shown that the ACTH(7-10) fragment has insignificant nootropic activity. Elongation of the molecule to ACTH (7)(8)(9)(10)(11)(12)(13)(14)(15)(16) leads to an increase in activity to a level comparable to ACTH(4-7) and ACTH (4)(5)(6)(7)(8)(9)(10) [3,4].…”

Section: Introductionmentioning

confidence: 99%

“…Animal experiments demonstrated that ACTH(6-9)PGP (FRWGPGP) exhibited nootropic and anxiolytic activities and enhanced the viability of cultured glial cells collected from the cerebral cortex of rats with ischemic stroke. Study of the effect of ACTH(6-9)PGP on the size of necrotic lesions in rats demonstrated an approximately 50% decrease in the size of the lesions in the course of ischemic stroke [8,9].…”

Section: Introductionmentioning

confidence: 99%

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ACTH(6-9)PGP Peptide Protects SH-SY5Y Cells from the H2O2, tert-Butyl Hydroperoxide, and Cyanide Cytotoxicity via Prolif-eration Stimulation and Antioxidant-related Genes Induction

Akimov¹,

Ev²,

Pv³

et al. 2021

Preprint

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Stabilized melanocortin analog peptide ACTH(6-9)PGP (FRWGPGP) possess a wide range of neuroprotective activities. However, its mechanism of action remains poorly understood. In this paper, we studied the pro-proliferative and cytoprotective activity of the adrenocorticotropic hormone fragment 6-9 (FRWG) linked with the peptide Prolyl-Glycyl-Proline on the SH-SY5Y cells in the model of oxidative stress-related toxicity. The peptide dose-dependently protected cells from H2O2, tert-butyl hydroperoxide, and KCN. The mechanism of its action was the modu-lation of proliferation-related (NF-kB and Nrf-2) and antioxidant-related (HO-1, Nqo1, Gclc) genes and apoptosis decrease.

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