Mutant of endotoxin neutralizing peptide and application thereof

Abstract

The invention discloses a mutant of an endotoxin neutralizing peptide, which is prepared by substituting at least two of the fifth, eighth, eleventh and fifteenth amino acid residues of the endotoxin neutralizing peptide consisting of the amino acid sequence represented by SEQ ID No. 1 with the following corresponding amino acid residues: alanine which substitutes lysine, namely the fifth amino acid residue; tryptophan which substitutes phenylalanine, namely the eighth amino acid residue; lysine which substitutes glutamine, namely the eleventh amino acid residue; and lysine which substitutes aspartic acid, namely the fifteenth amino acid residue. The mutant of the endotoxin neutralizing peptide of the invention can inhibit the combination of LBP and LPS by directly neutralizing competitiveness and activity of the LPS, inhibit an LPS induced excessive inflammatory response in vitro and in vivo, has a stronger function than aparental endotoxin-neutralizing peptide from the LBP, has no visible cytotoxicity and can be applied in the preparation of medicaments for preventing and treating endotoxin associated inflammations caused by Gram-negative bacterium infection.

Description

technical field [0001] The invention relates to a polypeptide, in particular to an endotoxin neutralizing peptide mutant, and also relates to the application of the polypeptide in medicine. Background technique [0002] Endotoxin / lipopolysaccharide (LPS) is the main component of the cell wall of Gram-negative bacteria. It is composed of core polysaccharides, O-polysaccharide side chains and lipid A. pathogenic factor. Lipopolysaccharide binding protein (LBP) is a key carrier protein that mediates the binding of LPS to the target cell surface receptor CD14. The induced inflammatory cascade reaction is amplified by 100-1000 times, which can lead to systemic inflammatory response syndrome, multiple organ failure and even death in severe cases. Therefore, inhibiting the catalytic amplification effect of LBP is one of the effective strategies to prevent and treat LPS-induced sepsis. [0003] The study of the relationship between structure and function of LBP shows that the ami...

AI Technical Summary

Problems solved by technology

However, the neutralizing LPS activity of the LPS binding site fragment of the above-mentioned LBP or its modified polypeptide still has a certain gap from the ideal neutralizing activity, and further improvement and improvement are needed.

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