Regulation of Gene Expression with Khavinson Peptides

It has been discovered that small peptides labeled with fluorescein isothiocyanate (FITC) can infiltrate the cytoplasm, nucleus, and nucleolus of HeLa cells. In eukaryotic cells, the nucleus possesses a nucleopore system, made up of protein complexes called nucleoporins, with an inner diameter of roughly 50 nm. These are permeable to diffusing molecules that weigh up to 3.5 kDa. Therefore, small peptides, based on their attributes such as size, charge, and hydrophobicity, can infiltrate the membranes of the cytoplasm and nucleus of cells and might interact with DNA.

Various physical techniques, such as UV spectroscopy, circular dichroism, viscosimetry, and atomic force microscopy, along with molecular modeling, have demonstrated that signal peptides can attach to DNA in a liquid medium. This binding process unfolds over several hours without much reliance on electrostatic forces. The interaction between DNA’s major groove and peptide causes an instability in the DNA’s secondary structure. Spectrophotometry results in the ultraviolet spectrum identified a concentration-dependent hyperchromic effect, providing evidence for a partial destruction of hydrogen bonds within the DNA double helix and a localized separation of the DNA chains.

Experiments have shown that the separation of synthetic DNA strands (melting) occurs at 69.50 C, but in the DNA-peptide system, melting occurs at 280 C. This change in temperature corresponds to a near two-fold decrease in enthalpy and entropy, pointing to a thermodynamically simpler way to melt DNA at temperatures suitable for most living organisms’ biochemical processes.

This information has allowed the proposal of a peptide-DNA interaction model, particularly with Khavinson peptides, and the creation of a stable DNA-peptide complex. A thorough examination of the complex’s physical and chemical characteristics was conducted through molecular modeling, leading to the creation of a three-dimensional interaction model.

Epigenetic Regulation of Gene Expression:

The discovery of particular binding of peptides with oligonucleotides has marked an exciting advance in our understanding of the epigenetic regulation of gene expression. This revelation is not only fascinating from a scientific standpoint but is potentially vital for medical and biological applications.

Peptide-Oligonucleotide Binding:

The interaction between peptides and oligonucleotides is a complex process that relies on the specific attributes of the peptides, such as their size, charge, and hydrophobicity. The unique binding of these small peptides to oligonucleotides can lead to a tailored control of gene expression, facilitating interactions with DNA in a specific and predictable manner.

Endonucleases and Aging Cells Modulation:

The article further explores the modulation of endonucleases in wheat seedlings by short peptides and the potential for control of DNA hydrolysis at the enzyme-peptide interaction level. The potential for peptides to activate heterochromatin in aging cells and the reversible nature of heterochromatinization with significant biological implications is also discussed.

Suppression and Elongation Effects on Genes:

Findings regarding the suppression of the HER-2/neu gene in transgenic mice and the elongation of telomeres in human lung fibroblasts through peptide administration are presented. The results also highlight the positive effects of specific peptides on expression in murine heart and brain genes and their regulatory impact on gene activity.

Impact on Human Health and Age-related Changes:

Various tetrapeptides were found to have significant impacts on gene expression in human bronchial epithelium and pancreatic cells, leading to positive health outcomes such as reduced chronic bronchitis. Age-related changes and peptide-induced modifications in methylation of promoter zones in specific genes were observed, potentially influencing gene expression levels.

Conclusion and Future Perspectives:

Finally, the article concludes that the tripeptide EDG has a regulating effect on mRNA expression in a rat model of induced gastric ulcers. The findings collectively point to the vital role of specific DNA-peptide interactions in early life stages and evolution, contributing to the epigenetic control of cellular function.