发明名称 |
MATRIX METALLOPROTEINASE INHIBITOR PEPTIDES |
摘要 |
The present invention is an isolated protein of 21,600 daltons which binds to both latent and activated type IV collagenase with high affinity at 1:1 molar stoichiometry, thereby abolishing enzyme activity. The protein is purified by affinity chromatography on solid phase metalloproteinase, or solid phase metalloproteinase substrates which bind the enzyme-inhibitor complex. The complete primary structure of this protein (initially called CSC-21K), as determined by sequencing overlapping peptides spanning the entire protein, reveals homology with a protein called TIMP, Tissue Inhibitor of Metalloproteinases. In addition, a cDNA for this novel inhibitor, now designated TIMP-2, was cloned from a melanoma cell and its sequence was compared with that of human TIMP-1. Northern blots of melanoma cell mRNA showed two distinct transcripts of 0.9 kb and 3.5 kb which are down-regulated by transforming growth factor-beta, and are unchanged by phorbol ester treatment. The figure 7 shows the cDNA and corresponding protein sequence of TIMP-2. |
申请公布号 |
WO9011287(A1) |
申请公布日期 |
1990.10.04 |
申请号 |
WO1990US01526 |
申请日期 |
1990.03.21 |
申请人 |
UNITED STATES OF AMERICA, REPRESENTED BY THE SECRE |
发明人 |
STETLER-STEVENSON, WILLIAM, G.;LIOTTA, LANCE, A.;KRUTZSH, HENRY |
分类号 |
A61K35/12;A61K38/00;A61K38/55;A61K39/395;A61K48/00;A61K49/00;A61P37/00;C07K1/16;C07K1/22;C07K7/08;C07K14/00;C07K14/81;C07K16/00;C12N1/21;C12N15/09;C12N15/15;C12P21/02;C12R1/91;G01N33/53;G01N33/573 |
主分类号 |
A61K35/12 |
代理机构 |
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代理人 |
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主权项 |
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地址 |
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