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

Yotam Lior, Efrat Shtriker, Shirin Kahremany, Eli C. Lewis, Arie Gruzman

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


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.

Original languageEnglish
Article number113969
JournalEuropean Journal of Medicinal Chemistry
StatePublished - 15 Jan 2022


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

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmacology
  • Organic Chemistry


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