Inhibition of Human Stromelysin by Peptides Based on the N-Terminal Domain of Tissue Inhibitor of Metalloproteinases-1

• Published in: Biochemical and biophysical research communications Vol. 205; no. 2; pp. 1156 - 1163
• Main Authors: Hanglow, A.C., Lugo, A., Walsky, R., Visnick, M., Coffey, J.W., Fotouhi, N.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.12.1994
• Subjects: Amino Acid Sequence; Glycoproteins - chemistry; Glycoproteins - pharmacology; Humans; Indicators and Reagents; Matrix Metalloproteinase 3; Matrix Metalloproteinase Inhibitors; Metalloendopeptidases - antagonists & inhibitors; Molecular Sequence Data; Oligopeptides - chemical synthesis; Oligopeptides - chemistry; Oligopeptides - pharmacology; Peptides - chemical synthesis; Peptides - chemistry; Peptides - pharmacology; Peptides, Cyclic - chemical synthesis; Peptides, Cyclic - chemistry; Peptides, Cyclic - pharmacology; Protein Structure, Secondary; Structure-Activity Relationship; Tissue Inhibitor of Metalloproteinases
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1006/bbrc.1994.2787

The tissue inhibitors of metalloproteinases (TIMPs) represent a family of naturally occurring protein inhibitors of stromelysin and other members of the family of matrix metalloproteinases. A series of peptides based on the N-terminal sequence of natural TIMP-1 was synthesized and assessed for inhibitory activity against purified human stromelysin. Inhibitor peptides were identified in the loop (bounded by the disulfide bonds [C 3-C 99] and [C 13-C 124]), e.g., [C 3(Acm)-C 13], (IC 50, 42 μM). It was established that inhibition was due to the free sulfhydryl group of either C 13 or C 124. However, peptides within [C 70(Acm)-C 98(Acm)] inhibited stromelysin independently of zinc co-ordination by cysteine. The binding epitope in TIMP-1 may be discontinuous and comprised of sequences from at least 2 loops.