Tumor necrosis factor (TNF)-alpha binding peptide and tumor necrosis factor receptor 1(TNFR1) blocking peptide and applications thereof in treatment of TNF related diseases

Abstract

The invention relates to a tumor necrosis factor receptor 1(TNFR1) blocking peptide and a TNFR1-Fc fusion protein formed by recombining the TNFR1 blocking peptide and a gene of an IgG1Fc segment. The TNFR1 blocking peptide is a 12-mer linear peptide. The invention also relates to a TNF binding cyclic peptide and a TNFR1 blocking cyclic peptide which are both cyclic 9 peptides (i.e. C7C), the TNFR1 blocking peptide, the TNFR1-Fc fusion protein, the TNF binding cyclic peptide, the TNFR1 blocking cyclic peptide and the like can competently inhibit the binding between the TNF-alpha and the TNFR1 no matter in vivo or vitro, thereby antagonizing the biological function of the TNF-alpha. And the TNFR1 blocking peptide, the TNFR1-Fc fusion protein, the TNF binding cyclic peptide, the TNFR1 blocking cyclic peptide and the like can obtain better treatment effects respectively on a rat model of adjuvant arthritis, a rat model of high fat and high glucose induced obesity and insulin-resistance and a rat model of trinitro-benzene-sulfonic acid (TNBS) induced experimental ulcerative colitis.

Description

technical field [0001] The invention relates to biotechnology, in particular to small molecular polypeptides such as TNF-binding peptides, TNFR1 blocking peptides and TNFR1 blocking peptide-Fc fusion proteins capable of antagonizing the biological activity of tumor necrosis factor-α (TNF-α). Background technique [0002] TNF-α is an important class of pro-inflammatory cytokines. freed. Clinical studies have confirmed that: in the occurrence and development of various infectious or non-infectious inflammations and their complications (such as autoimmune diseases such as rheumatoid arthritis, endotoxic shock, acute liver necrosis, Crohn's disease, etc.), systemic Or the increase of local TNF-α production plays a key role in inflammation; too high level of TNF-α in the body often indicates poor prognosis of patients. In animal experiments, a single application of large doses of TNF-α can directly lead to endotoxic shock, while anti-TNF antibodies can reduce and prevent the oc...

AI Technical Summary

Problems solved by technology

[0005] Although the above-mentioned commercialized anti-TNF-α reagents (anti-TNF antibody, soluble TNF receptor) have achieved good clinical therapeutic effects, there are still a series of problems, such as potential side effects, limited sources, poor biological stability, expensive etc.

At present, clinical trials have found that the above-mentioned anti-TNF-α reagents (anti-TNF antibodies, soluble TNF receptors) have side effects such as red blood cell and thrombocytopenia, tuberculosis infection, upper respiratory tract, urinary tract infection, rash, fever, hypo / hypertension, etc. Severe cases may cause tumors

Images