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

✍ Scribed by József Bódi; Nikolett Mihala; Andrea Hajnal; Katalin F. Medzihradszky; Dr Helga Süli-Vargha

• Book ID: 105360266
• Publisher: John Wiley and Sons
• Year: 2003
• Tongue: English
• Weight: 227 KB
• Volume: 9
• Category: Article
• ISSN: 1075-2617
• DOI: 10.1002/psc.455

✦ Synopsis

Abstract

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(Cys^145^‐Cys^166^) as a model—that mercury(II) ions can cause peptide degradation at pH 7.8 as well as in 0.1% trifluoroacetic acid. Copyright © 2003 European Peptide Society and John Wiley & Sons, Ltd.