Study On The Structure-Activity Relationship Of ?-Helix Peptide

With the widespread use of antibiotics and anticancer drugs,the problem of bacteria/tumor drug resistance has always been a difficult problem.It is urgent to develop a new type of drug with high efficiency,low toxicity,wide range of action and no easy resistance.Antimicrobial peptides have broad spectrum antibacterial activity,stable structure,and are not easy to produce drug resistance.They are expected to become a new type of antibacterial and antineoplastic agents.In this study,the?IIKK?₃-NH₂ molecule was used as a template in the laboratory to reconstruct the?IIKK?₃-NH₂ from the following four aspects:?1?keep the hydrophilic interface constant and increase the hydrophobic amino acid;?2?keep the hydrophobic interface unchanged and increase the number of hydrophilic amino acids;?3?The number of amino acids inserted at the hydrophilic interface is different and the number of charges is increased when the insertion number is the same;?4?whether the hydrophobic amino acids are arranged continuously.The physicochemical properties and biological activities of antibacterial peptides modified by these four aspects were studied,so we can investigate the structure activity relationship of peptides systematically.The circular two color spectrum showed that the peptides synthesized by our method are easy to form a helix structure in the hydrophobic environment,thus having antibacterial and anti-tumor activity.Through the study of physicochemical properties and biological activity of polypeptides,we found the following rules:keeping the hydrophilic interface of the polypeptide constant,increasing the number of hydrophobic amino acid of polypeptide can increase the antitumor activity of antitumor;When the hydrophobic interface is 8continuous hydrophobic amino acids,the increase of the number of hydrophilic amino acids in the polypeptide will reduce the gram negative bacteria and antitumor activity of peptides;The more hydrophobic amino acids are inserted into the hydrophilic surface,the more hydrophobic the polypeptide is;Keeping the number of hydrophobic amino acids in the water surface same,increasing the number of charges will reduce the hydrophobicity of peptides;When the hydrophilic interface is inserted into three amino acids,the antibacterial and antitumor activity is the best;The same number of hydrophilic interfaces will increase the antitumor activity of peptides;The same hydrophilic interface increases the number of charges will enhance the anti-tumor activity of peptides.Through this research,we can clarify the structure activity relationship of peptides,and provide theoretical basis and experimental support for the design of highly effective and low toxic antimicrobial peptides.