Synthesis of the C-terminal domain of the tissue inhibitor of metalloproteinases-1 (TIMP-1)

József Bódi, Nikolett Mihala, Andrea Hajnal, Katalin F. Medzihradszky, Helga Süli-Vargha

Research output: Contribution to journalArticle


According to recent investigations, the C-terminal domain of the tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) is responsible for some biological effects that are independent of the enzyme-inhibiting effect of the N-terminal domain of the molecule. The C-terminal domain has been prepared for structure-biological activity investigations. After the chemical synthesis and the folding of the linear peptide, LC-MS and MALDI-MS analysis revealed that two isomers with different disulphide bond arrangements were formed. Since more than 30 folding experiments resulted in products with a very similar HPLC-profile, it was concluded that in the absence of the TIMP-1 N-terminal domain no entirely correct folding of the C-terminal domain occurred. Furthermore, it was observed that, in spite of several purification steps, mercury(II) ions were bound to the 6SH-linear peptide; it was demonstrated - using disulphide bonded TIMP-1 (Cys145-Cys166) as a model - that mercury(II) ions can cause peptide degradation at pH 7.8 as well as in 0.1% trifluoroacetic acid.

Original languageEnglish
Pages (from-to)430-441
Number of pages12
JournalJournal of Peptide Science
Issue number7
Publication statusPublished - Jul 1 2003



  • C-terminal domain
  • Degradation
  • Disulphide-bridge
  • Mass spectrometry
  • Mercury(II) ions
  • Structural isomers
  • Synthesis
  • TIMP-1

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

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