Short Cell-Penetrating Peptides: A Model of Interactions with Gene Promoter Sites

Abstract

Analysis of the main parameters of molecular mechanics (number of hydrogen bonds, hydrophobic and electrostatic interactions, DNA-peptide complex minimization energy) provided the data to validate the previously proposed qualitative models of peptide-DNA interactions and to evaluate their quantitative characteristics. Based on these estimations, a three-dimensional model of Lys-Glu and Ala-Glu-Asp-Gly peptide interactions with DNA sites (GCAG and ATTTC) located in the promoter zones of genes encoding CD5, IL-2, MMP2, and Tram1 signal molecules.

Gastroprotective Oligopeptides

“…The advantages of the short peptides above their long-chain derivatives are high biological activity, that often many fold exceeds the activity of the peptide-precursor, high tissue specificity, lack of species specificity and lack of immunogenicity [13,14,[15][16][17][18]20,21]. It was established that low-weighing oligopeptides realize their effect on the cellular, chromosomal, genomic and molecular levels [13][14][15][16][17][18][19][20][21].…”

“…It was established that low-weighing oligopeptides realize their effect on the cellular, chromosomal, genomic and molecular levels [13][14][15][16][17][18][19][20][21]. The interaction with DNA was proposed to be the key moment of the realization of the biological effect of the short peptides [17][18][19]21].…”

“…This concept is supported by the data that the alterations in the peptidergic regulation of the body cause changes of the functional status of the cell, resulting in the decrease of gene expression and protein biosynthesis [13][14][15]17,18,21]. Oligopeptides were shown to be involved in the regulation of intracellular communication processes, nociception, vessel permeability, neoangiogenesis, nervous impulse transduction as well as affect the activity of hormones and enzymes and exhibit neuro-and immunomodulatory effects [13][14][15][16][17][18][19][20][21]. It is also hypothesized that biological activity of short peptides is mainly associated with their prominent antioxidant properties, although this data is a little bit contradictory as some compounds were reported to have an opposite effect, increasing the processes of oxidation [2,8,16,[24][25][26].…”

“…Thus, the mechanisms of peptidergic regulation of homeostasis open huge perspectives for the creation of the essentially new methods for the prevention and treatment of different diseases [13][14][15][16]. Interestingly, deep studies of the mechanisms of action of regulatory peptides showed that in many cases life-sustaining processes are regulated not by the total peptide molecules but their short-chained derivatives -oligopeptides that are produced in the course of limited proteolysis from proteins-precursors (cytokines, thymic peptides, immunoglobulins) [13,14,18,20,21].The term "oligopeptide" refers to proteins, composed of not more than 20 amino acid residues [22]. For example, it was shown that the inhibition of pancreatic juice secretion by 28-amino acidscontaining hormone ghrelin is realized by its biologically active part -pentapeptide with the sequence of amino acids Gly-Ser-Ser (n-octanoyl)-Phe [23].…”

“…Interestingly, deep studies of the mechanisms of action of regulatory peptides showed that in many cases life-sustaining processes are regulated not by the total peptide molecules but their short-chained derivatives -oligopeptides that are produced in the course of limited proteolysis from proteins-precursors (cytokines, thymic peptides, immunoglobulins) [13,14,18,20,21].…”