Binding ability of a thymine-functionalized oligolysine towards nucleic acids

Area of Science:

• Biochemistry
• Supramolecular Chemistry
• Nucleic Acid Chemistry

Background:

• Oligolysines are peptides with lysine residues.
• Nucleic acid interactions are crucial in biological systems.
• Functionalized peptides offer novel binding capabilities.

Purpose of the Study:

• To investigate the nucleic acid binding properties of a thymine-functionalized oligolysine.
• To characterize the binding stoichiometry and stability of nucleopeptide-nucleic acid complexes.
• To assess the stability of the nucleopeptide in human serum.

Main Methods:

• Circular dichroism (CD) spectroscopy
• UV-Vis spectroscopy
• Surface Plasmon Resonance (SPR)
• UV melting experiments
• CD titration
• Human serum stability assays

Main Results:

• The thymine-functionalized oligolysine is water-soluble and interacts with both DNA and RNA.
• Complexes formed with adenine-containing DNA (dA12) and RNA (rA12, poly rA) exhibit a 1:1 thymine/adenine (T/A) stoichiometric ratio.
• The nucleopeptide-RNA complex (with rA12) is more stable than the nucleopeptide-DNA complex (with dA12), likely due to RNA's 2'-OH groups.
• The nucleopeptide demonstrated a half-life of 45 minutes in human serum stability assays.

Conclusions:

• Thymine-functionalized oligolysine effectively binds to nucleic acids, forming stable complexes.
• The enhanced stability of the RNA complex highlights the role of specific interactions, such as those involving the 2'-OH group.
• The nucleopeptide exhibits moderate stability in human serum, suggesting potential for further development.