title: Synthesis of the C-terminal domain of the tissue inhibitor of metalloproteinases-1 (TIMP-1).
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(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.
authors.affiliation: Research Group for Peptide Chemistry, Hungarian Academy of Sciences, Eötvös Loránd University, H-1518 Budapest 112 PO Box 112, Hungary.
authors.forename: József
authors.initials: J
authors.lastname: Bódi
authors.forename: Nikolett
authors.initials: N
authors.lastname: Mihala
authors.forename: Andrea
authors.initials: A
authors.lastname: Hajnal
authors.forename: Katalin F
authors.initials: KF
authors.lastname: Medzihradszky
authors.forename: Helga
authors.initials: H
authors.lastname: Süli-Vargha
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D004220:Disulfides; D017669:Mercury Compounds / Q000737:chemistry; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D012016:Reference Values; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000138:chemical synthesis* / Q000737:chemistry*
chemical_list: D004220:Disulfides; D017669:Mercury Compounds; D019715:Tissue Inhibitor of Metalloproteinase-1