Retro-Inverso Collagen Modulator Peptide Derived from Serpin A1 with Enhanced Stability and Activity In Vitro.

Fosca Errante, Francesca Margheri, Lisa Giovannelli, Marco Pallecchi, Gianluca Bartolucci, Paolo Rovero, Elena Frediani, Anna M Papini

Journal: Journal of medicinal chemistry 2024;67(6):5053-5063

PMID: 38470817

Full Text on American Chemical Society View on PubMed

Abstract

The rising demand for novel cosmeceutical ingredients has highlighted peptides as a significant category. Based on the collagen turnover modulation properties of SA1-III, a decapeptide derived from a serine protease inhibitor (serpin A1), this study focused on designing shorter, second-generation peptides endowed with improved properties. A tetrapeptide candidate was further modified employing the retro-inverso approach that uses d-amino acids aiming to enhance peptide stability against dermal enzymes. Surprisingly, the modified peptide AAT11RI displayed notably high activity in vitro, as compared to its precursors, and suggested a mode of action based on the inhibition of collagen degradation. It is worth noting that AAT11RI showcases stability against dermal enzymes contained in human skin homogenates due to its rationally designed structure that hampers recognition by most proteases. The rational approach we embraced in this study underscored the added value of substantiated claims in the design of new cosmeceutical ingredients, representing a rarity in the field.

Address: Department of Neurosciences, Psychology, Drug Research and Child Health, University of Florence, Sesto Fiorentino, FI 50019, Italy.; Interdepartmental Laboratory of Peptide and Protein Chemistry and Biology, University of Florence, Sesto Fiorentino, FI 50019, Italy.; Espikem s.r.l., Prato, PO 59100, Italy.; Department of Neurosciences, Psychology, Drug Research and Child Health, University of Florence, Sesto Fiorentino, FI 50019, Italy.; Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, Firenze, FI 50139, Italy.; Department of Neurosciences, Psychology, Drug Research and Child Health, University of Florence, Firenze, FI 50139, Italy.; Interdepartmental Laboratory of Peptide and Protein Chemistry and Biology, University of Florence, Sesto Fiorentino, FI 50019, Italy.; Department of Chemistry "Ugo Schiff", University of Florence, Sesto Fiorentino, FI 50019, Italy.; Department of Neurosciences, Psychology, Drug Research and Child Health, University of Florence, Sesto Fiorentino, FI 50019, Italy.; Interdepartmental Laboratory of Peptide and Protein Chemistry and Biology, University of Florence, Sesto Fiorentino, FI 50019, Italy.

DOI: 10.1021/acs.jmedchem.4c00137

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https://doi.org/10.1021/acs.jmedchem.4c00137

MeSH Terms: Humans, alpha 1-Antitrypsin, Cosmeceuticals, Peptides, Collagen, Adjuvants, Immunologic