Targeting of Rage intracytoplasmic segment linker SLp76 and use of SAM

Abstract

A fusion protein of TAT and SAM functional domain of SLP76 protein has the effect of inhibiting inflammatory response during sepsis. The SAM functional domain of the SLP76 protein is brought into the cell through the cell-penetrating peptide TAT, competitively binds to the cytoplasmic segment of the RAGE receptor, and antagonizes the interaction between RAGE and the endogenous adapter protein SLP76 during the development of sepsis It can reduce the release of inflammatory factors in the process of sepsis by mediated cell signal transduction, so as to play a role in treating sepsis or improving prognosis. The SAM functional domain fusion protein of TAT and SLP76 protein can be used as a targeted drug for sepsis treatment. It is a polypeptide that directly passes through the cell membrane and enters the cell in a non-classical endocytic manner. Its important feature is that it can carry a variety of different sizes and properties. biologically active substances into cells.

Description

technical field [0001] The invention belongs to the field of biomedicine, and particularly relates to the use of a SAM functional domain targeting RAGE intracytoplasmic segment adapter protein SLP76 (SH2 domain containing leukocyte protein of 76kDa) as a drug for treating RAGE-related inflammatory diseases. Background technique [0002] Sepsis is a systemic inflammatory response syndrome (SIRS) caused by pathogenic microorganism infection. It is a common complication in critically ill patients after severe trauma, burns, and major surgery. septic shock), acute respiratory distress syndrome (acuterespiratory distress syndrome, ARDS) and multiple organ dysfunction syndrome (multiple organdysfunction syndrome, MODS). The incidence of sepsis is high. There are more than 18 million cases of severe sepsis every year in the world, and this number is still increasing at a rate of 1.5% to 8.0% per year. Epidemiological surveys show that the fatality rate of sepsis has surpassed that...

AI Technical Summary

Problems solved by technology

However, neither the TLR4 receptor itself nor the TLR4 signal transduction pathway, nor the intervention of anti-cytokines (TNF-α, IL-1, etc.) can significantly improve sepsis in clinical treatment of sepsis patients. patient survival time

[0005] Although the current studies on multiple interventions in various aspects of TLRs have achieved satisfactory results in animal experiments, unfortunately none of the experimental results have passed phase III clinical research so far, so looking for new treatments for sepsis Strategies are particularly urgent and important

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