Design, synthesis and evaluation of biomimetic affinity ligands for elastases

Hörour Filippusson*, Lýður S. Erlendsson, Christopher R. Lowe

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


A low-molecular-weight biomimetic affinity ligand selective for binding elastase has been designed and synthesized. The ligand was based on mimicking part of the interaction between a natural inhibitor, turkey ovomucoid inhibitor and elastase, and modelled from the X-ray crystallographic structure of the enzymeinhibitor complex. Limited solid-phase combinatorial chemistry was used to synthesize 12 variants of the lead ligand using the triazine moiety as the scaffold for assembly. The ligand library was screened for its ability to bind elastase and trypsin, and two ligands were studied further. Ligand C4/6 [2-alanyl-alanyl-4-tryptamino-6-(α-lysyl)-s-triazine] was found to bind porcine pancreatic elastase, but not trypsin, with a dissociation constant of 6 x 10-5 M and a binding capacity of 21 mg elastase per ml gel. The adsorbent was used to purify elastase from a crude extract of porcine pancreas. Immobilized ligand C4/5 6 [2-alanylalanyl-4-tyramino-6-(α-lysyl)-s-triazine] was similarly chosen for optimal binding of elastase from cod and used to purify the enzyme from a crude extract of cod pyloric caeca. Ligand C4/6 was subsequently synthesized in solution and its structure verified by 1H-NMR. Copyright (C) 2000 John Wiley and Sons, Ltd.

Original languageEnglish
Pages (from-to)370-381
Number of pages12
JournalJournal of Molecular Recognition
Issue number6
Publication statusPublished - 2000

Other keywords

  • Affinity chromatography
  • Biomimetic ligands
  • Elastase
  • Serine proteinase
  • Triazine


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