Systematic search for structural motifs of peptide binding to double-stranded DNA

Abstract

A large variety of short biologically active peptides possesses antioxidant, antibacterial, antitumour, anti-ageing and anti-inflammatory activity, involved in the regulation of neuro-immuno-endocrine system functions, cell apoptosis, proliferation and differentiation. Therefore, the mechanisms of their biological activity are attracting increasing attention not only in modern molecular biology, biochemistry and biophysics, but also in pharmacology and medicine. In this work, we systematically analysed the ability of dipeptides (all possible combinations of the 20 standard amino acids) to bind all possible combinations of tetra-nucleotides in the central part of dsDNA in the classic B-form using molecular docking and molecular dynamics. The vast majority of the dipeptides were found to be unable to bind dsDNA. However, we were able to identify 57 low-energy dipeptide complexes with peptide-dsDNA possessing high selectivity for DNA binding. The analysis of the dsDNA complexes with dipeptides with free and blocked N- and C-terminus showed that selective peptide binding to dsDNA can increase dramatically with the peptide length.

EDR Peptide: Possible Mechanism of Gene Expression and Protein Synthesis Regulation Involved in the Pathogenesis of Alzheimer’s Disease

“…Long-term studies have revealed the selective nature of short peptides’ activity (tissue- and gene-specific) [ 101 ]. To explain the target mechanism of peptide regulation of gene expression and protein synthesis, models of the interaction of short peptides with DNA and histone proteins have been proposed [ 102 , 103 ]. These models provide means for the explanation of the high biological activity of ultrashort peptides.…”

“…It was established that the EDR peptide possessed neuroprotective properties when administered orally in patients with traumatic brain injury and cerebrosthenia, as well as in experimental neuropathology induced by hypoxia and oxidative stress in AD and Huntington’s disease models in vitro. Presumably, the molecular mechanism of the EDR peptide biological activity, like a number of other short peptides, is associated with its ability to penetrate into the cytoplasm and the cell nucleus [ 106 ] and regulate gene expression and synthesis of the corresponding proteins [ 88 , 103 , 104 ].…”

Peptide Regulation of Gene Expression: A Systematic Review

“…Another study using molecular modeling methods analyzed the ability of all 400 dipeptide variants (all possible combinations of 20 standard amino acids) to bind all possible combinations of double-stranded DNA tetranucleotides (dsDNA) in the classical B-form. Among all the options, 57 dipeptides were identified with high selectivity of binding to dsDNA [80]. The authors noted that blocking at the ends of the dipeptides with the standard capping groups N-(CH3-CO-NH-) and C-(-CO-NH2) increases the binding performance.…”

Peptides: Prospects for Use in the Treatment of COVID-19

“…This peptide is capable of selective binding to the TCGA sequence of double-stranded DNA and manifests anticarcinogenic, antioxidant and geroprotective properties. It was shown that the KE peptide regulates the expression of the EPS15, MCM10 homologue, Culline 5, APG5L, FUSED, ZNF01, FLJ12848 fis, ITPK1, SLC7A6, FLJ22439 fis, KIAA69799, FIA, KIAA690099, FLA2 peptides, FLJ10914, Gdap1, MSTP028, MLLT3 and PEPP2, and the synthesis of cytoskeleton proteins, cell proliferation and metabolism, which explains its high biological activity [ 103 ]. The tetrapeptide AEDG (Epitalon) stimulates the activity of the neuroimmunoendocrine system, normalizing the functions of the thymus and cardiovascular system in pathology and ageing through regulation of melatonin synthesis [ 104 ].…”