Studies On Design, Synthesis And Molecular Recognition Of Cyclic Peptides Containing Polyamine, Disulfide Or Thioether Structure

The study on molecular recognition of cyclic pep tide is one of the frontiers in bioorganic chemistry. In this dissertation the efforts were focused on design and synthesis of cyclic peptides containing polyamine, disulfide bond or thioether and their molecular recognition as well as enantioselective recognition. A series of useful and creative results have been obtained.Six cyclic peptides containing polyamine, five cyclic peptides containing disulfide bond and ten cyclic peptides containing thioether have been designed and synthesized. The synthetic methods of the target compounds have been systematically investigated. A series of convenient and efficient reaction have been developed. An efficient 1+1 cyclization method was employed for the preparation of cyclic peptide. All these cyclic peptides possess different recognition sites, different rigidity and flexibility and different chiral centers. Their structures were confirmed by 1HNMR, MS and element analyses.Molecular recognition properties of these cyclic peptides for amino acid methyl ester hydrochloride were examined by UV-visible titration. The binding constants (K_α) and Gibbs free energy changes (-AGo) were determined. The 1HNMR spectra were used to elucidate further the recognition abilities. The results show that 1:1 complexes were formed for the cyclic peptides with the guests examined. The driving forces of molecular recognition mainly come fromhydrogen bond formed by the amino group and carbonyl in guest and carbonyl and amide in host. The most of the cyclic peptides were favorable for binding with D-amino acid methyl ester hydrochloride. At the same time, the rigidity and flexibility of the host, micro-environmental effects changed by the side chain also play important roles in the recognition process. 1HNMR study show that the amide linkage could act as donor of hydrogen bond as well as receptor of hydrogen bond.Molecular recognition properties of these cyclic peptides for cations and anions were also examined by UV-visible titration and the binding constants (K) and Gibbs free energy changes (-AGo) were determined. The results show that the cyclic peptides containing disulfide bond or thioether could act as good receptor of cations as well as good receptor of anions. The drive forces mainly come from static electricity allurement and cation interaction. The strength of interaction of an artificial cyclic peptide with cations should depend not only on the radius but also on the charge of the cation, cyclic peptides often showed high binding affinity for cations of high charge and small radius.