What is it about?
Recombinant human TIMP-2 a critical resource for further pharmacological and pre-clinical evaluation. This was previously not achieved due to high GC content of 5' region of TIMP-2 cDNA and absence of streamlined purification strategies. This study reports for the first time optimization of coding sequence leading to incresed production yield and two step purification strategy that can be scaled up. Further the purified TIMP-2 was characterized by biophysical methods, could effectively inhibit metalloprotease and proliferation of cancer cells in-vitro.
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Why is it important?
Rapid and uncontrolled degradation of the extracellular matrix (matrix that surrounds tissues) is a characteristic of several disease state like rheumatoid arthritis, macular degeneration and metastatic cancer. This degradation releases growth factors trapped in it leading to faster degradation and growth of new blood vessels (angionenesis) in metastatic cancer. With no metalloprotease inhibitors in the market, TIMP-2 is an attractive metalloprotease inhibitor. It has also showed inhibition growth factor responsive cancer cell/tumor growth making it a unique dual active biotherapeutic candidate. We have for the first time, using combination of methods , been able to produce and characterize rec. human TIMP-2 that is being used in pre-clinical studies.
Perspectives
Apart from enabling pre-clinical studies we were also able to carry out in-depth biophysical characterization of TIMP-2 by 2 dimensional NMR that paves the way for further future protein engineering.
Dr. Ananda Chowdhury
National Cancer Institute, National Institutes of Health
Read the Original
This page is a summary of: Tissue Inhibitor of Metalloprotease-2 (TIMP-2): Bioprocess Development, Physicochemical, Biochemical, and Biological Characterization of Highly Expressed Recombinant Protein, Biochemistry, November 2017, American Chemical Society (ACS),
DOI: 10.1021/acs.biochem.7b00700.
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