Stapled peptide, and preparation method and pharmaceutical application thereof

Abstract

The invention relates to the field of biological medicine, in particular to stapled peptide and a preparation method and pharmaceutical application thereof. Specifically, the present application relates to a stapled peptide comprising a main chain amino acid sequence selected from the following: (a) an amino acid sequence as shown in IHVIIPADLWDWINK (SEQ ID NO: 1); (b) an amino acid sequence having at least 80%, 86.7% or 93% sequence identity with SEQ ID NO: 1; or (c) an added or substituted amino acid sequence having one, two or three amino acid residues compared to SEQ ID NO: 1; amino acid residues at the ith position and the (i + 3) th position, or amino acid residues at the ith position and the (i + 4) th position, or amino acid residues at the ith position and the (i + 7) th position of a main chain of the stapled peptide are coupled into a ring through a linker, and the linker comprises at least one amino acid; i is an integer greater than or equal to 1. The stapled peptides can be used for the treatment of diseases associated with the overexpression of IL-17A.

Description

technical field [0001] The present application relates to the field of biomedicine, in particular to stapled peptides, their preparation methods and their pharmaceutical uses. Background technique [0002] Interleukin-17A (IL-17A) is a cytokine with a wide range of biological functions, which acts on a variety of cells downstream of the inflammation regulation process, mediates different physiological processes and produces corresponding biological effects. Studies have found that IL-17A is associated with a variety of autoinflammatory diseases (AID) and autoimmune diseases (AD) such as psoriasis (PsO), ankylosing spondylitis (AS), rheumatoid arthritis (RA), silver Psoriatic arthritis (PsA), multiple sclerosis (MS), and Crohn's disease (CD) are associated and could be targets for the treatment of these diseases. [0003] In recent years, peptide drugs have become one of the fastest growing fields in the pharmaceutical industry. Compared with small molecule drugs, peptide d...

AI Technical Summary

Problems solved by technology

Compared with small molecule drugs, peptide drugs have higher target affinity and lower systemic toxicity, but due to the lack of protein backbone support, peptide drugs are more likely to lose their natural structural conformation in solution, resulting in reduced activity

In addition, compared with proteins, polypeptides have a smaller size, which allows them to obtain higher biomembrane penetration, but also brings many obstacles to drugability, such as easier enzymatic degradation and filtered by glomeruli

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