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

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.

Neuroprotective Effects of Tripeptides-Epigenetic Regulators in Mouse Model of Alzheimer's Disease.

KED and EDR peptides prevent dendritic spines loss in amyloid synaptotoxicity in in vitro model of Alzheimer's disease (AD). The objective of this paper was to study epigenetic mechanisms of EDR and KED peptides' neuroprotective effects on neuroplasticity and dendritic spine morphology in an AD mouse model. Daily intraperitoneal administration of the KED peptide in 5xFAD mice from 2 to 4 months of age at a concentration of 400 µg/kg tended to increase neuroplasticity. KED and EDR peptides prevented dendritic spine loss in 5xFAD-M mice. Their action's possible molecular mechanisms were investigated by molecular modeling and docking of peptides in dsDNA, containing all possible combinations of hexanucleotide sequences. Similar DNA sequences were found in the lowest-energy complexes of the studied peptides with DNA in the classical B-form. EDR peptide has binding sites in the promoter region of CASP3, NES, GAP43, APOE, SOD2, PPARA, PPARG, GDX1 genes. Protein products of these genes are involved in AD pathogenesis. The neuroprotective effect of EDR and KED peptides in AD can be defined by their ability to prevent dendritic spine elimination and neuroplasticity impairments at the molecular epigenetic level.

Composites based on heparin and MIL-101(Fe): the drug releasing depot for anticoagulant therapy and advanced medical nanofabrication.

We describe the synthesis and properties of a new composite material based on heparin and MIL-101(Fe) metal-organic framework. The intrinsic instability of MIL-101(Fe) towards hydrolysis enables binding of heparin molecules to the framework structure as is evidenced by DFT calculations and adsorption experiments. The de novo formed heparin-MOF composites showed good biocompatibility in in vitro and demonstrated pronounced anticoagulant activity. The specific interaction between the bioactive molecule and the carrier is critical for the selective degradation of the complex in the body fluids and for the enhanced activity. Hep_MIL-101(Fe) composite could serve as a drug-releasing depot for nanofabrication and to introduce anticoagulant activity to medical devices and biocoatings. Addition of Hep_MIL-101(Fe) to a sol-gel derived thrombolytic matrix allowed the combination of anticoagulant and thrombolytic activities in a single hybrid nanomaterial that could be applied as a bioactive nanocoating for PTFE vein implants.