Degradation of the ACTH(4-10) analog Semax in the presence of rat basal forebrain cell cultures and plasma membranes

Zolotarev, Yu. A.; Долотов, О. В.; Иноземцева, Л. С.; Dadayan, A. K.; Dorokhova, E. M.; Andreeva, L. A.; Alfeeva, L. Yu.; Гривенников, И. А.; Myasoedov, N. F.

doi:10.1007/s00726-006-0328-8

Cited by 13 publications

(7 citation statements)

References 14 publications

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“…Also, the proteolysis of simple glyprolines by enzymes and nasal slime, brain membranes, and rat blood have been determined via “in vitro” experiments . Unlike proteolytic processes in the blood, the peptides generated in the brain are commonly products of the N‐terminal proteolysis of the initial heptapeptide . All obtained data (proteolytic and physiological experiments) let us to select the group of peptides that is most likely forms the general totality of biologically active Semax synacton peptides in the brain.…”

Section: Resultsmentioning

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: Resultsmentioning

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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“…However, the cleavage of the peptide containing the N terminus is more intense. The main route of degradation is the cleavage of the C-and Nterminal dipeptides, to form the pentapeptides His-Phe-Pro-Gly-Pro and Met-Glu-His-Phe-Pro [91]. Thus, as a result of fairly rapid enzymatic degradation, Semax in brain tissues is a mixture of peptide derivatives with different compositions [92].…”

Section: Pharmacokineticsmentioning

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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“…The HSCIE reaction makes it possible to produce uniformly tritium-labeled peptides 108 for use both in receptor binding analysis [109][110][111][112] and for the determination of their peptidase biodegradation paths in ViVo and in Vitro. [113][114][115] It has been shown that these uniformly tritium labeled peptides completely retain their biological activity. 116,117 The theoretical analysis of hydrogen exchange in the CtxG1 polypeptide revealed some important HSCIE features regarding the influence of peptide chain mobility on the reactivity of amino acids (Figure 20; Table 16).…”

Section: Hscie Reaction With Peptides and Proteinsmentioning

confidence: 99%