Antibacterial polypeptide compound, synthesis method and application thereof

Abstract

The invention belongs to the field of medicinal chemistry, and particularly relates to a Sar-modified high-stability antibacterial polypeptide compound based on an antibacterial peptide polybia-MPI. The invention provides a Sar-modified antibacterial polypeptide compound [Sar2]-MPI based on the antibacterial peptide polybia-MPI, a synthesis method thereof and application of the antibacterial polypeptide in preparation of antibacterial drugs, wherein the Sar-modified antibacterial polypeptide compound [Sar2]-MPI has high stability, good antibacterial activity and low toxicity. According to the invention, through a more systematic scanning and screening method, key sites influencing the in-vivo stability in a polypeptide sequence are found in a more similar physiological environment, and screening and action mechanism research on the stability, in-vivo and in-vitro antibacterial activity and toxic and side effects are carried out on a replaced analogue, so that a novel antibacterial drug with improved stability and antibacterial activity and reduced toxicity is obtained.

Description

technical field [0001] The invention belongs to the field of medicinal chemistry, and in particular relates to a Sar-modified high-stable antibacterial polypeptide compound based on the antibacterial peptide polybia-MPI, a synthesis method of the antibacterial polypeptide and its application in the preparation of antibacterial drugs. Background technique [0002] The discovery of antibiotics has effectively controlled infectious diseases and greatly reduced the risk of medical procedures such as surgery. However, with the misuse and abuse of antibiotics, bacterial resistance has become a global problem that threatens human health, and the research and development of new antibiotic drugs has stagnated. In recent years, almost no new antibiotic drugs have been launched. When more and more " When "superbugs" continue to appear, people are faced with the situation that there is no drug available, so it is an extremely urgent task to develop new antibiotics that are not easy to c...

AI Technical Summary

Problems solved by technology

Yanyan Zhao et al. used D-Lys to replace Lys in the polybia-MPI sequence, and obtained the analog D-Lys-MPI. Although the plasma stability has been improved, it is accompanied by antibacterial activity because the configuration change of the replacement site affects the spatial conformation of the polypeptide molecule. In addition, the analogue D-MPI obtained by replacing all D-type amino acids has improved plasma stability while retaining antibacterial activity, but the cost of D-type amino acids is much higher than that of L-type amino acids, to a large extent Increased modification cost of peptides

Beijun Liu et al. carried out intramolecular cyclization of polybia-MPI to improve stability, but the obtained analogs either had decreased antibacterial activity or showed higher hemolytic side effects

In addition, the composition and function of proteases in plasma are very complex, including multiple families of plasmin, cysteine ​​protease, serine protease, exoprotease, matrix metalloprotease, and only individual specific proteases such as trypsin and chymotrypsin are used There are still deficiencies in studying the in vivo stability of polypeptide molecules, and it is necessary to develop more systematic research methods for the real environment in vivo

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