Design,Synthesis,and Bioactivity Of Small Molecule Antibacterial Peptides

The annual number of bacterial infections in the world is as high as 1.5 billion,with a death rate of 4.6 million,particularly high mortality due to multidrug resistance(MDRB)infection,which is a serious threat to public health;Europe and the United States each year due to bacterial infection prevention and control expenditure Up to 7 billion euros and $ 6.5billion,while developing countries are required to bear a higher price for this.Antibacterial peptide(AMP)is a kind of peptide material which is produced by the organism to resist the invasion of exogenous pathogens.It is also an important part of natural immunity,and has the basic structural features of cationic and amphiphilic.Compared with traditional antibiotics,AMP has a series of advantages,such as antibacterial spectrum,rapid sterilization and low antibiotic resistance,and it is expected to develop a new type of antimicrobial agent with high efficiency and low toxicity.A small molecular polypeptide with high antimicrobial activity,low hemolytic activity,low cytotoxicity and good stability was screened by three technical methods of rational design,efficient screening and experimental verification of small molecule antimicrobial peptides.Based on the antimicrobial peptide sequence,the predominant amino acid and the dominant locus,the virtual combination design of antimicrobial peptides was carried out by using the antimicrobial peptide LfcinB64-9(RRWQWR)as template,and the high-throughput small molecule polypeptide was realized by quantitative structure-activity relationship analysis Screening,the specific experimental steps are as follows:1 ? Based on the structure-activity relationship of amino acid sequence analysis,the polypeptide sequence was collected from the polypeptide database APD2,and LfcinB64-9 was used as template to modify it based on sequence pattern,dominant amino acid and dominant site.2 ? 14 selected candidate small molecule antibacterial peptides and template peptide LfcinB64-9 were chemically synthesized,purified and identified by mass spectrometry.3 ? small molecule antibacterial peptide biological activity experiments,including:antimicrobial peptides antibacterial test,erythrocyte hemolytic toxicity test,cytotoxicity test,the stability of the peptide in plasma test,liposome rupture test.Through the above experiment for the next step to lay a certain foundation for peptide drugs.The main research achievements of this subject are as follows:1?To establish the synthetic route of small molecule antimicrobial peptides to complete the transformation of unnatural amino acid sequence.2 ? this study selected three(RWRWRW,RRWWRF,RRWWRW)high antibacterial activity,small side effects,good stability of small molecules antimicrobial peptides,which RRWWRW of Acinetobacter baumannii has a good antibacterial effect,its minimum Antibacterial concentration of 16?g/ml,and at 512?g/ml when the cytotoxicity and erythrocyte lysis activity of less than 5%.In this study,we established a theoretical model for the combination of AMP design and virtual screening,and provided a complete technical scheme for the rational design and efficient screening of small molecule antimicrobial peptides.The antibacterial activity of Aminobacter baumannii was strong and the stability was good.High-molecular-weight antimicrobial peptides,lay the foundation for the design and development of new low-resistant peptide antibiotics.At the same time,the use of computer-aided drug design method to guide the design and screening of antimicrobial peptides,not only can get a variety of highly active antimicrobial peptide molecules,and can improve the screening speed and reduce research costs.