The Success of Good Old and Highly Specific Separation Method in the Isolation of Bioactive Proteins: From Bench to Bedside
DOI:
https://doi.org/10.9734/bpi/nicb/v2/11825DKeywords:
Ligand affinity chromatography, soluble receptor, binding protein, IL-6R, IFN-\(\gamma\)R, TNFRI, TNFRII, TBPI, TBPII, Enbrel\({^T}{^M}\), Type I Interferon Receptor, IFN-\(\alpha\)/\(\beta\)R, IFNAR2, IL-18, IL-18 binding protein, IL-18BP, Tadekinig alfa\({^T}{^M}\), IL-32, proteinase 3, resistin, heparanase, serendipityAbstract
My approach of combining a rich source of human proteins (500-fold concentrated human urine) with a highly specific isolation method, the ligand-affinity-chromatography, enabled rapid and efficient isolation of not only soluble receptors, but also independent binding-proteins and associated enzymes. Using this approach, the following soluble form of several receptors as well as binding proteins were isolated: IL-6R, TNFRI, TNFRII, Type I Interferon receptor (IFN-\(\alpha\)/\(\beta\)R), Type II Interferon receptor (IFN-\(\gamma\)R), IL-18 Binding Protein (IL-18BP) and IL-32 Binding Protein. These findings enabled to coin the concept that soluble receptors and binding proteins are normal constituents of body fluids in healthy individuals and their levels in pathological situations are modulated. Moreover, the identification of soluble receptors led to the cloning of their long-sought cell surface ligand-binding counterparts. A number of the soluble proteins translated into drugs.
