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Screening Model And Rhubarb To For Restructuring Hsil-1r Άρ, And Hstnfr Target High-throughput Antagonist Of Hil-1r Άρ, Antagonistic Component Of Chemical Research

Posted on:2001-02-07Degree:DoctorType:Dissertation
Country:ChinaCandidate:Q W LiFull Text:PDF
GTID:1114360185469436Subject:Microbial and Biochemical Pharmacy
Abstract/Summary:PDF Full Text Request
Interleukin-1 (IL-1), which takes part in many physiological and pathological processes, is a kind of important cytokine. It' s effects are exerted mainly via IL-1 receptor type I (EL-1R I). Soluble forms of IL-1R can be produced fiom proteolytic cleavage of the extracellular portion of the cell surface. Tumor necrosis factor (TNF) is an other kind of important immuno-regulatory factor which effects are exerted mainly via 55 kD TNF receptor. The proteolytic cleavage of 55 kD receptor can produce soluble TNFR with a molecular weight of 27-33 kD. Both of the two receptors have the ability to bind with their own ligands.In this study, hsIL-1R I and hsTNFR proteins were obtained from recombinant Streptomyces lividans (pSGLgpp/sIL-1R I ) and S. lividans [pIJ459-mel/sTNFR] separately. After the supernatant of recombinant Streptomyces lividans was precipitated with ammonium sulfate, dialyzed and separated with anion exchange chromotography, the preliminary purified recombinant receptors were obtained. Two antagonist screening models were developed respectively with hsIL-1R and hsTNFR as targets based on fee competitive receptor-ligand interactions.Using the IL-1R antagonists model, 500 microorganisms strains were screened for three times ,the positive ratio is about 6.4%. With the hsTNFR antagonist screening model ,anofeer 500 strains were screened also for three times, the positive ratio is about 0.4%.The hsIL-1R antagonist active components of Rheum officinale were trailed with the hsIL-1R antagonist screening model and seven kinds of active compounds were isolated. Their chemical structures were elucidated wife chemical - physical analysis and spectroscopic analysis as following : emodin, chrysophanol , rhein, aloe-emodin, Rheosmine, catechin-3-O-gallate, 6-cinnamoyllindleyin. From them, rheosmine and 6-cinnamoyllindleyin were first isolate from Rheum officinale.The hsIL-1R antagonists activities of all the above compounds were found for the first time.
Keywords/Search Tags:High-throughput
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