Catalytically active peptides affected by self-assembly and residues order

Area of Science:

• Biochemistry
• Peptide Chemistry
• Catalysis

Background:

• Amphiphilic peptides offer robust, synthetic alternatives to natural enzymes.
• Designed peptides are explored to mimic enzyme functions, such as serine proteases.
• Amino acid sequence motifs can dictate peptide conformation and function.

Purpose of the Study:

• To investigate how the arrangement of catalytic triad residues affects the self-assembly and catalytic activity of amphiphilic peptides.
• To evaluate the hydrolysis efficiency of designed peptides mimicking serine protease activity.

Main Methods:

• Synthesized three β-sheet amphiphilic peptides with varying orders of glutamate, histidine, and serine.
• Assessed the catalytic hydrolysis efficiency of these peptides using p-nitrophenyl acetate (pNPA) as a substrate.

Main Results:

• Peptide sequence significantly influenced both peptide assembly structures and catalytic performance.
• The peptide Ac-Cys-Phe-Glu-Phe-Ser-Phe-His-Phe-Pro-NH2 (ESH) exhibited the highest catalytic efficiency (0.19 M⁻¹ s⁻¹) at 250 μM.
• Intermolecular interactions of charged active site residues can stabilize assemblies but potentially reduce catalytic activity.

Conclusions:

• The order of catalytic triad residues is a critical, often overlooked, factor in designing effective catalytic amphiphilic peptides.
• Optimizing residue arrangement can enhance catalytic efficiency by balancing assembly stabilization and active site accessibility.
• This work provides insights for the rational design of artificial enzymes based on peptide assemblies.