The Solid Phase Strategy Of Several Oligopeptides And It's Interaction Of Oligopeptides With DNA

Oligopeptides compounds generally have strong biological activity, and most of them can be used as drugs or drug precursors. The studies on the interaction and structure-activity relationships of drugs, drug leads and drug candidates with DNA can help us to understand the mechanism of drugs on molecular level and to provide guidance for the design of drugs. This thesis consists of the following points:1 Two types of peptides were synthesised by Fmoc-based solid-phase strategy. One was lysine-rich cationic peptides (Lys)₄-Cys and Cys-(Lys)₅-Ala, the other was antioxidant peptides Ala-His-His, Ala-His-Lys,β-Ala-His, Leu-Lys-Tyr. Cys-(Lys)₄, Cys-(Lys)₅-Ala and Ala-His-His are new compounds, Such solid-phase strategy that was used to prepare Ala-His-Lys,β-Ala-His,Leu-Lys-Tyr has not been reported.2 The two cationic peptides were purified and prepared by reverse-phase high performance liquid chromatography (RP-HPLC) in C18 column. The purity of the (Lys)₄-Cys and Cys-(Lys)₅-Ala products was 96.1%, 97.33%, respectively.3 The six peptides were characterized by IR, ESI-MS, ¹H NMR and ¹³C NMR. The structures were as followed. 4 The interaction of the six peptides with calf thymus DNA was investigated by ultraviolet visible absorption spectrometry, fluorescence spectroscopy, viscosity measurements and gel electrophoresis techniques.(1) The results showed that there was an strong interaction between the two cationic peptides and DNA. The binding mode mainly was partial intercalative interaction. The binding constants were 2.53×10⁴ L·mol^-1 and 3.15×10⁴ L·mol^-1, respectively; The fluorescence quenching constants were 2.83×10⁴ L·mol^-1 and 8.98×10⁴ L·mol^-1 , respectively. It is speculated that the positive charge of peptide surface would electrostaticly combine with the negatively charged phosphate groups of DNA, which woule lead to the charge of their structure and conveniently intercalate to the base of DNA.(2) The experimental results show that the four antioxidant peptides can bind to DNA. The interaction is as followed, Leu-Lys-Tyr>Ala-His-Lys>β-Ala-His>Ala-His-His. The binding mode of the Ala-His-His, Ala-His-Lys andβ-Ala-His with calf thymus DNA was electrostatic or groove binding and not intercalation. The binding mode of the Leu-Lys-Try with calf thymus DNA was partial intercalation or electrostatic binding.5 The result of anticancer activity showed that the cationic peptides has anti-tumor activity. The finding woule provid a theoretic basis for the anticancer drug screening...