4.6 Article

Screening of anti-atrophic peptides by using photo-cleavable peptide array and 96-well scale contractile human skeletal muscle atrophy models

Journal

BIOTECHNOLOGY AND BIOENGINEERING
Volume 119, Issue 8, Pages 2196-2205

Publisher

WILEY
DOI: 10.1002/bit.28125

Keywords

contractile force; microdevices; organ-on-a-chip; phenotypic screening; tissue engineering

Funding

  1. Japan Society for the Promotion of Science

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This study successfully screened peptides with anti-atrophic activity using photo-cleavable peptide array technology and a 96-well screening system. The results suggest that this screening approach is a powerful method for obtaining anti-atrophic peptides and that the 96-well screening system and atrophic model are practical tools for drug/functional food ingredient development.
Skeletal muscle atrophy is characterized by decreases in protein content, myofiber diameter, and contractile force generation. As muscle atrophy worsens the quality of life, the development of anti-atrophic substances is desirable. In this study, we aimed to demonstrate a screening process for anti-atrophic peptides using photo-cleavable peptide array technology and human contractile atrophic muscle models. We developed a 96-well system and established a screening process with less variability. Dexamethasone-induced human atrophic tissue was constructed in the system. Eight peptides were selected from the literature and used for the screening of peptides for preventing the decrease of the contractile forces of tissues. The peptide QIGFIW, which showed preventive activity, was selected as the seed sequence. As a result of amino acid substitution, we obtained QIGFIQ as a peptide with higher anti-atrophic activity. These results indicate that the combinatorial use of the photo-cleavable peptide array technology and 96-well screening system could comprise a powerful approach to obtaining anti-atrophic peptides, and suggest that the 96-well screening system and atrophic model represent a practical and powerful tool for the development of drugs/functional food ingredients.

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