ANGT_HUMAN[448-462], an Anorexigenic Peptide Identified Using Plasma Peptidomics

Area of Science:

• Biochemistry and Molecular Biology
• Peptidomics and Drug Discovery
• Neuroendocrinology and Metabolism

Background:

• Bioactive peptides are crucial for understanding human disease pathophysiology and serve as leads for novel drug development.
• Plasma peptidomics has identified numerous native peptides, offering a rich source for functional screening and target identification.
• Cell-surface protein interactions of peptides are key to their biological functions and therapeutic potential.

Purpose of the Study:

• To identify novel bioactive peptides from human plasma peptidomics data with potential therapeutic applications.
• To elucidate the cell-surface binding proteins and biological functions of a newly identified proangiotensinogen-derived peptide.
• To investigate the potential of this peptide as an anorexigenic agent and its mechanism of action.

Main Methods:

• Synthesis and functional screening of native peptides identified via plasma peptidomics using human cultured cells.
• Cell-surface binding assays using fluorescently labeled and biotinylated peptides to identify target proteins via LC-MS/MS.
• In vivo studies in mice to assess the peptide's effect on food/water intake and locomotor activity following different administration routes.

Main Results:

• A 15-amino acid peptide, ANGT_HUMAN[448-462], derived from proangiotensinogen, demonstrated cellular responses and cell binding.
• The β-subunit of ATP synthase was identified as the cell-surface binding protein for ANGT_HUMAN[448-462].
• ANGT_HUMAN[448-462] significantly suppressed food and water intake in mice at low doses without affecting motor activity, indicating anorexigenic properties.

Conclusions:

• ANGT_HUMAN[448-462] is a novel anorexigenic peptide that binds to the β-subunit of ATP synthase on cell surfaces.
• The peptide's ability to modulate eating behavior suggests its potential role in regulating energy homeostasis.
• This study highlights the utility of plasma peptidomics and functional screening in discovering bioactive peptides for therapeutic development.