Design An Antibacterial Peptide By Studying On Granulysin's Antibacterial Mechanism

Antibacterial peptide is a kind of peptide secreted by insects and has antibacterial activities. People have not found that the bacteria can resist against the antibacterial peptides by now, according to this fact, the antibacterial peptides have greatly applicable valuation. So by studying the mechanism of those special peptides and combining with the analyses of their structures, sequences, we can construct an ideal peptide with supposed higher activities for the aim of clinical application. Cell-immunity reaction is an important way for man to resist against the bacterial intrusion, during this process, a kind of significant protein—cytotoxic protein, plays a significant role. Fortunately, Granulysin is a special peptide that has been found recently and belongs to the cytotoxic proteins, its mRNA was found by researchers in Stanford University twenty years ago. It has a broad range of activity against epiphyte, parasites, Gram-negative, Gram-positive and so on. Because Granulysin is secreted in the human body, and has little bio-toxicity, therefore, on the basis of its activity mechanism, we can reconstruct its active structure to design a peptide, which is supposed to have a higher activity. Meanwhile, we can verify our results by means of bio-computing and traditional experiments. 1 Firstly, we use the data such as three-dimensional structure and sequence in some Bio Databases, for example PDB and SwissProt, to simulate the model of Granulysin's acting with membrane, and then make clear some significant factors such as Granulysin's active structure, basic amino-acids, hydrophobic amino-acids and static electro-potential; 2 Secondly we tried to design a peptide segment by replacing some important amino-acids. First step, we used Arguslab to theoretically verify our result by bio-computing, showing that in the N-terminal area, the static electro-potential is stronger and wider than original segment; in addition, the designed segment expresses higher amphipath characteristic; furthermore, after replacing, Phe have higher hydrophobic characteristic and then is supposed to more easily intrude into the membrane. 3 Thirdly, we synthesized this segment using HOBT/DCC method, and got the aimed peptide by G-25 separating; at last, we could be further to verify our result by the experiments of activity-analysis. By now, we can say that on the background of developments of Bio-informatics and more and more Bio-information shared all over the world, the method of combing the molecular simulation with traditional experiments in the molecular level is sure to be promising.