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- Title
MODELING, SYNTHESIS AND IN VITRO SCREENING OF UNUSUAL AMINO ACIDS AND PEPTIDES AS PROTEASE INHIBITORS.
- Authors
Sargsyan, Armen; Hakobyan, Heghine; Mardiyan, Zorayr; Jamharyan, Silva; Dadayan, Ani; Sargsyan, Tatevik; Hovhannisyan, Nelli
- Abstract
Currently non-proteinogenic amino acids and synthetic peptides are widely used as building blocks in the drugs design. Many of these compounds are enzyme inhibitors or antimicrobials. Secreted Clostridium histolyticum collagenase is considered as a virulence factor and thus is an attractive target for fighting microbial infection. Trypsin is a target for the treatment of digestive disorders. This study was aimed to find new inhibitors of collagenase and trypsin. The interaction of non-proteinogenic amino acids and peptides with C. histolyticum collagenase and trypsin has been evaluated by Molecular Docking followed by the measurement of enzyme inhibition by selected compounds. According to the Docking analysis, N-tert-butoxycarbonylglycyl-(S)-2-amino-3-(4-((4-fluorophenyl)-ethynyl)-phenyl)-α-alanine has to demonstrate the most effective interaction with collagenase. Thus, the synthesis of this dipeptide was carried out. Measurement of enzymes activity revealed that both the dipeptide and the amino acid included in its structure inhibit collagenase and trypsin. The amino acid inhibited collagenase with IC50 = 0.32 mM and trypsin with IC50 = 0.57 mM. The dipeptide inhibited collagenase with IC50 = 0.62 mM and trypsin with IC50 = 89 uM. Keywords: bacterial collagenase, molecular docking, inhibitor, peptide synthesis.
- Subjects
COLLAGENASES; DIPEPTIDES; AMINO acids; TRYPSIN; PEPTIDES; PROTEASE inhibitors; PEPTIDOMIMETICS
- Publication
Journal of Chemical Technology & Metallurgy, 2023, Vol 58, Issue 3, p615
- ISSN
1314-7471
- Publication type
Article
- DOI
10.59957/jctm.v58i3.93