Pascarella Simona, Tiberi Caterina, Sabatino Giuseppina, Nuti Francesca, Papini Anna Maria, Giovannelli Lisa, Rovero Paolo
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.
Laboratory of Peptide and Protein Chemistry & Biology, Department of Chemistry, University of Florence, via della Lastruccia 3-13, 50019, Sesto Fiorentino, Italy.
ChemMedChem. 2016 Aug 19;11(16):1850-5. doi: 10.1002/cmdc.201500472. Epub 2015 Nov 30.
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.
在治疗诸如胶原相关疾病和皮肤老化等病理或病理生理状况的背景下，调节胶原蛋白周转可能是一个相关的药理学靶点。我们最近的工作集中在寻找短链肽作为先导化合物，以进一步开发增强I型胶原蛋白产生的化合物。在本研究中，我们选择并合成了丝氨酸蛋白酶抑制剂A1（Serpin A1）C端部分（残基393 - 418）的重叠肽，其对胶原蛋白产生的影响先前已有报道，目的是鉴定更短且仍具活性的片段，并深入了解其中涉及的机制。用培养的正常人皮肤成纤维细胞评估每个片段的生物活性，并通过我们自行开发的夹心ELISA技术监测收集到的培养基中胶原蛋白含量的变化。有趣的是，我们鉴定出一种十肽，称为SA1-III（Ac-MGKVVNPTQK-NH2），作为符合我们目的的有前景的候选物；它能够在微摩尔浓度下使处理细胞的培养基中I型胶原蛋白水平显著增加。
