PEGylated MOTS-c

PEGylated MOTS-c is a modified form of the mitochondrial-derived peptide MOTS-c conjugated with polyethylene glycol (PEG) to extend its plasma half-life and improve systemic distribution. Native MOTS-c is rapidly cleared from circulation, limiting its utility for in vivo research requiring sustained exposure.

MOTS-c is a naturally occurring mitochondrial-encoded peptide that functions as an exercise mimetic, activating AMPK and improving insulin sensitivity and glucose homeostasis. However, its short half-life has been a significant limitation for translational research applications.

The PEG modification increases molecular size, reducing renal filtration and providing steric protection against proteolytic degradation. This extends the effective half-life from minutes to hours or days, depending on PEG size, enabling study of chronic MOTS-c exposure effects that would otherwise require continuous infusion.

PEGylated MOTS-c is particularly valuable for research into age-related metabolic decline, where MOTS-c levels naturally decrease with aging. The extended-duration formulation allows investigation of whether sustained MOTS-c replacement can restore youthful metabolic parameters, improve exercise capacity in aged subjects, or provide protection against metabolic diseases in long-term studies.