α-Helical Peptides Encoded in Collagen Exhibit Antimicrobial Activity with Low Cytotoxicity

Area of Science:

• Biochemistry
• Immunology
• Drug Discovery

Background:

• Endogenous antimicrobial peptides (AMPs) are crucial for innate immunity.
• Host proteins are an underexplored source of AMPs.
• Extracellular matrix collagens contain latent AMPs within nonfibrous domains.

Purpose of the Study:

• To investigate collagen proteins as a source of endogenous antimicrobial peptides (AMPs).
• To identify and characterize novel AMPs derived from collagen's nonfibrous domains.
• To evaluate the bioactivity and biocompatibility of collagen-derived AMPs.

Main Methods:

• In silico mining of collagen sequences prioritizing physicochemical properties (net charge, Boman index, hydrophobic moment).
• Synthesis and experimental evaluation of predicted α-helical AMP candidates.
• Comparison of collagen-derived AMPs with benchmark AMPs and machine learning-predicted peptides.

Main Results:

• Identified 107 predicted α-helical AMP candidates from collagen sequences.
• Three collagen-derived peptides demonstrated broad-spectrum antimicrobial activity against bacterial and fungal pathogens.
• Collagen-derived peptides showed significantly reduced cytotoxicity toward human cells compared to their antimicrobial efficacy.

Conclusions:

• Nonfibrous domains of extracellular matrix collagens represent a reservoir of endogenous AMPs.
• Collagen-derived AMPs exhibit potent antimicrobial activity and favorable biocompatibility.
• These findings highlight collagen-derived AMPs as promising scaffolds for antimicrobial drug discovery.