title: Serpin A1 C-Terminal Peptides as Collagen Turnover Modulators.
abstract: The modulation of collagen turnover can be a relevant pharmacological target in the context of treating either pathological or pathophysiological conditions, such as collagen-related diseases and skin aging. Our recent work has focused on the search for short-chain peptides as lead compounds for further development of compounds that enhance the production of type I collagen. In this study we selected and synthesized overlapping peptides of the C-terminal portion of serpin A1 (residues 393-418), the impact of which on collagen production has been reported previously, in order to identify shorter and still active fragments and to provide insight on the mechanisms involved. The biological activity of each fragment was evaluated with cultured normal human dermal fibroblasts, and changes in the amounts of collagen were monitored in collected culture media by a sandwich ELISA technique developed in house. Interestingly, we identified a decapeptide, termed SA1-III (Ac-MGKVVNPTQK-NH2 ), as a promising candidate for our purposes; it is able to induce a significant increase in type I collagen levels in the culture medium of treated cells at micromolar concentrations.
authors.affiliation: Laboratory of Peptide and Protein Chemistry & Biology, Department of NeuroFarBa, Section of Pharmaceutical Sciences and Nutraceutics, University of Florence, via Ugo Schiff 6, 50019, Sesto Fiorentino, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Pascarella
authors.affiliation: Laboratory of Peptide and Protein Chemistry & Biology, Department of NeuroFarBa, Section of Pharmaceutical Sciences and Nutraceutics, University of Florence, via Ugo Schiff 6, 50019, Sesto Fiorentino, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Tiberi
authors.affiliation: Laboratory of Peptide and Protein Chemistry & Biology, Department of Chemistry, University of Florence, via della Lastruccia 3-13, 50019, Sesto Fiorentino, Italy.|Espikem Srl, via F. Ferrucci 203/c, 59100, Prato, Italy.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Sabatino
authors.affiliation: Laboratory of Peptide and Protein Chemistry & Biology, Department of Chemistry, University of Florence, via della Lastruccia 3-13, 50019, Sesto Fiorentino, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Nuti
authors.affiliation: Laboratory of Peptide and Protein Chemistry & Biology, Department of Chemistry, University of Florence, via della Lastruccia 3-13, 50019, Sesto Fiorentino, Italy.|PeptLab@UCP & LCB/EA4505, University of Cergy-Pontoise, 5 Mail Gay Lussac, 95031, Cergy-Pontoise CEDEX, France.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Papini
authors.affiliation: Department of NeuroFarBa, Section of Pharmacology and Toxicology, University of Florence, Viale Pieraccini 6, 50139, Firenze, Italy. lisa.giovannelli@unifi.it.
authors.forename: Lisa
authors.initials: L
authors.lastname: Giovannelli
authors.affiliation: Laboratory of Peptide and Protein Chemistry & Biology, Department of NeuroFarBa, Section of Pharmaceutical Sciences and Nutraceutics, University of Florence, via Ugo Schiff 6, 50019, Sesto Fiorentino, Italy. rovero@unifi.it.
authors.forename: Paolo
authors.initials: P
authors.lastname: Rovero
mesh_terms: D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D012867:Skin / Q000378:metabolism; D000515:alpha 1-Antitrypsin / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: C043392:SERPINA1 protein, human; D000515:alpha 1-Antitrypsin; D003094:Collagen
keywords: biological activity; collagen; peptides; serpin A1; wound healing