Structure Of AABB Series Helical Peptides And Their Biological Activity

Since discovery and application of penicillin,antibiotics have saved countless lives and improved the quality of human life.But they have aggravated the resistance of pathogenic microorganisms.In order to deal with"Superbugs",it is required to standardize the clinical use of antibiotics and develop new antibacterial drugs.Antimicrobial peptides are small molecules with broad-spectrum antimicrobial and they are parts of the innate immune defense system among all classes of lives.In addition,antimicrobial peptides have been found to be efficient in killing fungi,viruses and even cancerous cells.Their activity depends on several factors including the sequence,size,structure,positive charge,hydrophobicity and amphipathy.In this research,based on the common features of natural antimicrobial peptides,a series of peptides have been designed by using the template of(AABB)_n.To study the influence of differences of the hydrophilic amino acid side chains and the hydrophilic/hydrophobic regions on the biological activity of the peptides,the template sequence is modified by substitution or deletion of amino acids.These peptides were synthesized by SPPS method and were investigated about many properties,including secondary structure,surface activity,antibacterial and antitumor activity,cytotoxicity and immune response and bacterial resistance.Circular dichroism spectra have demonstrated that hydrophilic amino acid side chains have no effect on the secondary structure formation of peptides.All of these peptides were able to formα-helical structure in hydrophobic environment.Hydrophilic amino acid side chains can affect biological activity of peptides.There are no significant influence on biological activity when lysines were replaced by arginines on the peptide sequence.However,there was dramatic decline on biological activity when lysines replaced by histidines on the peptide sequence.The hydrophilic and hydrophobic regions of helical structure can affect the biological activity of these peptides.There are no biological activity when hydrophobic amino acids were removed.There are no significant influence on the biological activity when one residue in the hydrophobic region of the helical peptide was replaced by a hydrophilic amino acid residue.The detection of the bacterial resistance has indicated that the bacterial does not show resistance to the peptide,and the expression of the bacterial resistance gene was suppressed by the peptide.