Study Of 2460A And 2520A As Human Interleukin 6 Receptor Antagonists

Interleukin 6 (IL-6), which displays a broad range biological activities on many kinds of cells, such as lymphocytes, hematopoietic stem cells, liver cells, tumor cells and neuronal cells, is a kind of important cytokine. Additionally, IL-6 is involved in many pathology processes of disease such as inflammation, rheumatoid arthritis, tumor, Castleman's disease and autoimmune diseases. Especially, it is reported that the level of IL-6 is very high in the cell of myeloma. IL-6 exhibits its role on target cells through a double-stranded receptor complex consisting of IL-6R and a signal transduction subunit (gpl30). IL-6R is one of transmembrane glycoprotein which has two types of natural receptors: gpl30 binding with membrane and soluble IL-6R. Both of them play essential role during the process of IL-6 signal transduction.With the recombinant IL-6R as target, an ELISA assay for screening antagonists of IL-6R was developed by us. Using this method, two antagonist of IL-6R was isolated from the cultured broth of the strains.There are two parts in the project.In the first part, the metabolites of Fungal sp. Trichoderma hazianum have been well studied. Using the IL-6R antagonist screening model, an antagonist of IL-6R was isolated from the fermentation supernatant of the strain named as Fungal sp. Trichoderma hazianum. The compound was named 2460A and the molecular formula and structure were elucidatited through UV, IR, ESI-MS, HRMS, NMR. 2460A was identified a new structure .In this paper, we describe the fermentation, isolation, structural elucidation and biological activity...