Lipidated Stapled Peptides Targeting the Acyl Binding Protein UNC119

Area of Science:

• Biochemistry
• Cell Biology
• Molecular Medicine

Background:

• UNC119 proteins bind and transport N-myristoylated proteins, essential for cellular functions.
• UNC119a is specifically vital for the completion of cytokinesis, the process of cell division.

Purpose of the Study:

• To design and generate novel lipidated, stabilized alpha-helical peptides that specifically target UNC119a.
• To investigate the potential of these peptides as inhibitors of UNC119a function and consequently, cytokinesis.

Main Methods:

• Utilized a lipidated peptide derived from Gnat1, a UNC119 binding partner.
• Employed hydrocarbon peptide-stapling techniques to create stabilized, cell-permeable peptide binders.
• Assessed the effect of the generated peptides on cell cycle progression and morphology.

Main Results:

• Successfully designed and synthesized cell-permeable peptide binders targeting UNC119a.
• Observed the accumulation of cells in cytokinetic arrest and formation of binucleated cells upon treatment.
• Demonstrated that these peptides disrupt normal UNC119a-mediated processes.

Conclusions:

• UNC119a is a viable therapeutic target for the inhibition of cytokinesis.
• Lipidated, stabilized alpha-helical peptides are effective tools for targeting UNC119a.
• This approach offers a potential strategy for developing novel anti-cancer or anti-parasitic agents.