Linker peptide for constructing fusion protein

Abstract

The invention provides a linker peptide for constructing a fusion protein, comprising a flexible peptide and a rigid peptide; the flexible peptide is composed of one or more flexible units, and the rigid peptide is composed of one or more rigid units, wherein each flexible unit comprises two or more amino acid residues selected from Gly, Ser, Ala and Thr, and each ridge unit comprises a plurality of glycosylation-sited carboxyl-terminal peptides (CTP) of human chorionic gonadotrophin beta-subunit. The linker peptide herein is more efficient in eliminating steric-hindrance effect between two fusion molecules, and reducing polymerization or activity decrease or loss due to misfolding or comformational change of active proteins; in addition, negatively-charged high-sialyl CTPs can resist removal by kidney, half-life period of the fusion molecules is further extended, bioavailability of the fusion protein is improved; more additionally, protection from glycosyl side chains of the CTPs enables reduced sensitivity of the linker peptide to protease such that the fusion protein is rarely degraded in a linker region.

Description

technical field [0001] The present invention relates to the field of fusion protein, more specifically, relates to a connecting peptide used for constructing fusion protein. Background technique [0002] In the past two decades, protein fusion technology has been widely used in the construction of bifunctional antibodies, bifunctional enzymes and bifunctional proteins. However, various problems have been encountered in the process of constructing fusion proteins, such as proteins that can be folded correctly when expressed alone cannot be folded correctly in the fusion protein; the two fused proteins are shielded due to the close spatial distance; the fusion Protein molecules are easily degraded by proteases due to incorrect folding or conformational changes; protein catalytic domains that originally had a certain degree of flexibility lose their original functions after fusion, etc. The emergence of these problems often leads to reduced or even complete loss of fusion prot...

AI Technical Summary

Problems solved by technology

However, various problems have been encountered in the process of constructing fusion proteins, such as proteins that can be folded correctly when expressed alone cannot be folded correctly in the fusion protein; the two fused proteins are shielded due to the close spatial distance; the fusion Protein molecules are easily degraded by proteases due to incorrect folding or conformational changes; originally flexible protein catalytic domains lose their original functions after fusion, etc.

The emergence of these problems often leads to reduced or even complete loss of fusion protein activity

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