Research Of The Interaction Between Cyclic Dipeptides And Monovalent Metal Ions

Cyclic peptides, a kind of biological molecules composed by amino acid unit and with special character, widely exist in nature and exhibit a multitude of interesting biological activities. Cyclic peptides are playing more and more important role in biological modeling, pharmaceutical design, nano-and molecular devices, biological sensors and catalysts on account of their stable structural characteristics. Because of special spatial configurations, cyclic peptides have shown broad potentials in many areas including chemistry, pharmaceutical chemistry, biochemistry, and life sciences. In this thesis, the reaction of amino acids assembling into cyclic dipeptides directed by phosphorus trichloride was studied in detail. Moreover, a series of amino acid cyclic peptides were synthesized and isolated by different configurations. At the same time, HPLC was used to study the contents of different configuration of cyclic dipeptides product by differ-method, and the preliminary reason has been carried out.On the basis of our previous work, the idea of template synthesis was introduced to explore new synthesis method of cyclic peptide. Using quaternary ammonium salt as template, cyclic peptides of Leucine and Valine were synthesized and the promoting effect of the template was investigated by HPLC-ESI-MS. The results showed that the tetramethyl ammonium iodide might be an efficient template agent for cyclic peptide synthesis, especialy for cyclic peptides of Leucine and Valine.The interaction of cyclic dipeptides with metal ions was examined by NMR, HPLC, ESI-MS and UV. At the same time, the influence of mobile phase composition on association constant(Ka) has been investigated by HPLC. The results showed that the binding ability of cis-conformation cyclic peptides with metal ion was stronger than trans-configuration in both conditions except for phenylalanine cyclic dipeptides. In addition, the cyclic peptides compounds had stronger binding ability with Na+ and Ag+ ions than other monovalent metal ions. Furthermore, it was found that the association constant was improved with the increasing of water content in mobile phase. Using ESI-MS, the association constants in different temperature were acquired. By measuring the thermodynamic parameters of binding process of cyclic dipeptide and metal ion, the interacting force between cyclic dipeptide and metal ion was presumed to be hydrophobic force. The calculating results obtained were in good agreement with those obtaining by HPLC and UV. NMR results showed that trans-conformation of the methionine cyclic peptides on silver ion had a strong recognition interaction. Generally, the binding abilities of metal ion to cis-cyclic dipeptide are higher than that of trans-configuration and the affinity of Ag+ to Phenylalanine cyclic dipeptide is higher than that of Tyrosine or Tryptophan cyclic dipeptide.