C-Terminal Nucleobase Modification Amplifies Peptide-Mediated Liposome Fusion.

Area of Science:

• Biochemistry
• Biotechnology
• Nanotechnology

Background:

• Fusion peptides are essential for membrane fusion processes, crucial in biotechnology and medicine.
• Current fusion peptides, often derived from viral proteins, have limited versatility.
• Developing novel fusion peptides with enhanced properties is a key research area.

Purpose of the Study:

• To investigate the effect of end-capping a cationic helical peptide with a nucleobase on its liposome fusion capabilities.
• To explore a new strategy for designing potent fusion peptides beyond viral protein fragments.

Main Methods:

• Synthesized a cationic helical peptide analog (Oct-K2569Tric-Lol) and its nucleobase-modified version (Oct-K2569Tric-T).
• Investigated the peptides' effect on negatively charged liposomes using concentration-dependent aggregation and fusion assays.
• Examined the role of complementary nucleobases at peptide termini in promoting membrane fusion.

Main Results:

• The unmodified peptide induced reversible liposome aggregation.
• C-terminal thymine nucleobase addition transformed the peptide's activity to irreversible membrane fusion.
• Complementary nucleobases at both peptide termini promoted membrane fusion efficiently, even without membrane leakage.

Conclusions:

• End-capping cationic helical peptides with nucleobases is a viable strategy to enhance membrane fusion.
• This approach offers a versatile platform for designing novel fusion peptides for various applications.
• Findings pave the way for improved drug delivery, cell biology research, and nanotechnology tools.