Fusion peptide for treating autoimmune disease
PDL1-pHLIP, a preparation method of the PDL1-pHLIP, and an application of the PDL1-pHLIP in treatment of autoimmune diseases are provided. A fusion peptide is prepared by binding a pH low insertion peptide and an extracellular domain of PDL1. The pH low insertion peptide may be inserted onto a cell membrane of a focus tissue in an acid environment; the PDL1 bound to the pH low insertion peptide is subjected to targeting localization at the focus by utilizing the above properties of the pH low insertion peptide; a PD-1/PD-L1 negative signal of the focus tissue is enhanced by utilizing the pH low insertion peptide; and immune response of effector T cells is suppressed at the source, thereby achieving an effect of preventing and treating the autoimmune diseases.
1 . A fusion peptide of a pH low insertion peptide, comprising a pH low insertion peptide and an immune checkpoint ligand, wherein:
the pH low insertion peptide comprises an extracellular domain sequence repeating by one or more times;
the extracellular domain sequence consists of one of the amino acid sequences of SEQ ID NO: 1-17;
the immune checkpoint ligand comprises an extracellular domain of the PD-L1;
the extracellular domain of the PD-L1 comprises the amino acid sequence of SEQ ID NO: 18 or SEQ ID NO: 19; and
the extracellular domain of the PD-L1 is bound to an N-terminus of the pH low insertion peptide through a linker.
2 . The fusion peptide according to claim 1 , wherein the linker comprises the amino acid sequence represented by (X) m , X consists of the sequence of SEQ ID NO: 29 or SEQ ID NO: 30, and m is an integer of 1-10.
3 . The fusion peptide according to claim 2 , wherein X consists of the sequence of SEQ ID NO: 29.
4 . The fusion peptide according to claim 1 , wherein the fusion peptide comprises one of the amino acid sequences of SEQ ID NO: 20-22.
5 . A pharmaceutical composition, comprising the fusion peptide according to claim 1 .
6 . A marker system, comprising the fusion peptide according to claim 1 .
7 . A method for treating rheumatoid arthritis, comprising: administering an effective amount of the fusion peptide according to claim 1 to a patient in need thereof.
8 . A method for treating rheumatoid arthritis, comprising: administering an effective amount of the pharmaceutical composition according to claim 5 to a patient in need thereof.