2. Academic Validation
  3. Development of anti-inflammatory peptidomimetics based on the structure of human alpha1-antitrypsin

Development of anti-inflammatory peptidomimetics based on the structure of human alpha1-antitrypsin

  • Eur J Med Chem. 2022 Jan 15;228:113969. doi: 10.1016/j.ejmech.2021.113969.
Yotam Lior 1,  Efrat Shtriker 2,  Shirin Kahremany 3,  Eli C Lewis 1,  Arie Gruzman 4
Affiliations

Affiliations

  • 1 Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
  • 2 Department of Chemistry, Faculty of Exact Sciences, Bar-Ilan University, Ramat Gan, 5290002, Israel.
  • 3 Department of Chemistry, Faculty of Exact Sciences, Bar-Ilan University, Ramat Gan, 5290002, Israel; The Skin Research Institute, The Dead Sea and Arava Science Center, 86910, Masada, Israel.
  • 4 Department of Chemistry, Faculty of Exact Sciences, Bar-Ilan University, Ramat Gan, 5290002, Israel. Electronic address: gruzmaa@biu.ac.il.
PMID: 34763945 DOI: 10.1016/j.ejmech.2021.113969
Abstract

Human α1-antitrypsin (hAAT) has two distinguishing functions: anti-protease activity and regulation of the immune system. In the present study we hypothesized that those two protein functions are mediated by different structural domains on the hAAT surface. Indeed, such biologically active immunoregulatory sites (not associated with canonical anti-protease activity) on the surface of hAAT were identified by in silico methods. Several Peptides were derived from those immunoregulatory sites. Four Peptides exhibited impressive biological effects in pharmacological concentration ranges. Peptidomimetic (14) was developed, based on the structure of the most druggable and active peptide. The compound exhibited a potent anti-inflammatory activity in vitro and in vivo. Such a compound could be used as a basis for developing novel anti-inflammatory drug candidates and as a research tool for better understanding hAAT functions.

Keywords

Anti-inflammatory drug candidates; Bio-active peptides; Human α1-antitrypsin; Peptidomimetics.

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