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Development of Myostatin Inhibitory d-Peptides to Enhance the Potency, Increasing Skeletal Muscle Mass in Mice. | LitMetric

Myostatin is a key negative regulator of skeletal muscle growth, and myostatin inhibitors are attractive tools for the treatment of muscular atrophy. Previously, we reported a series of 14-29-mer peptide myostatin inhibitors, including a potent derivative, MIPE-1686, a 16-mer N-terminal-free l-peptide with three unnatural amino acids and a propensity to form β-sheets. However, the biological stability of MIPE-1686 is a concern for its development as a drug. In the present study, to develop a more stable myostatin inhibitory d-peptide (MID), we synthesized various versions of a 16-mer peptide. Among these, an arginine-containing derivative, MID-35, shows a potent and equivalent myostatin inhibitory activity equivalent to that of MIPE-1686 and considerable stability against biodegradation. The potency of MID-35 to increase the tibialis anterior muscle mass in mice is significantly enhanced over that of MIPE-1686, and MID-35 can serve as a new entity for the prolonged inactivation of myostatin in skeletal muscle.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8919388PMC
http://dx.doi.org/10.1021/acsmedchemlett.1c00705DOI Listing

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