The Activity Study Of Antimicrobial Peptide With Thioxopeptide Bond

Tumor has become the number one threat to human health,but the therapy of tumor is still a worldwide medical problem.Traditional treatment methods,such as: radiation therapy,chemotherapy and surgical treatment,more or less have their own limitations and great side effects.As a result,searching for new anti-tumor medicines with good activities and low side effects has become the new focus of tumor therapy.Recently,the possibility of antimicrobial peptides used as a new anti-tumor drug has been proved.But the poor stability,the cytotoxicity and high production costs made it hard for antimicrobial peptides to be used during the stage of clinical research.We designed three antimicrobial peptides with thioxopeptide bond for the purpose to increase the activities and stabilities,their sequences are as follows:MPI:Ile-Asp-Trp-Lys-Lys-Leu-Leu-Asp-Ala-Ala-Lys-Gln-Ile-Leu-NH₂MPI-1:Ile-Asp-Trp-Lys-Lys-Leu-Leu-Asp-Ala-Ala-Lys-Gln-Ile-LeuΨ-NH₂MPI-2:IleΨ-Asp-Trp-Lys-Lys-Leu-Leu-Asp-Ala-Ala-Lys-Gln-Ile-Leu-NH₂MPI belongs to the mastoparan family.Compared with other peptides of this family,MPI has the best selective.MPI-1,MPI-2 have different thioxopeptide bonds replace sites.Peptides with thioxopeptide bonds have high stability,low toxicity, which made peptides play its activities bettler.The results indicated that,compared with MPI,analogues MPI-1,MPI-2 have increased anti-tumor activities against HEPG-2,PC-3 and EJ cell lines.Similarly, MPI-1 and MPI-2 have stronger stability than MPI.Further more,the hemolytic of two analogues is stronger than MPI,which may be the result of the increase of their hydrophobic.The in vivo anti-tumor activity of these peptides also confirmed the increased anti-tumor activity.In summary,antimicrobial peptides with thioxopeptide bonds have increased anti-tumor activity and stability,and this kind of peptides have the prospect to be potential anti-tumor drugs.