Synthesis Of Ace-inhibitory Peptides Analog By Solid-phase Method And Reciprocity With DNA

Peptides compounds generally have strong biological activity, and most can be used as drugs or prodrugs. DNA is the carrier of genetic information. Its molecular structure and properties are closely related with temperature, pH, solution concentration and other environmental factors. The studies on the interaction of oligopeptides compounds with DNA can help to understand the mechanism of drugs on molecular level, and provide guidance for the design of more effective drugs on clinical. Therefore, the studies on the interaction of oligopeptides compounds with DNA have great theoretical significance and application value in chemistry, biology and medicine.In this paper, the peptides of Arg-Leu-Pro,His-Arg-Arg-Cys,Lys-Lys-Arg-Lys-Val-Cys,Ala-Ala-Ala-Ala-His-His-Ala-Cys was synthesized by solid phase method, using Wang resin as the solid phase carrier, Fmoc as theα-amino protection group and HBTU-HOBT as the condensation agent. The crude products were purified by RP-HPLC. The products were characterized by ESI-MS,¹H NMR and¹³CNMR.The interaction between peptides and DNA were investigated by using ultraviolet visible absorption spectrometry (UV-Vis), fluorescence spectroscopy and viscosity measurement. The effects of different factors on the interaction were studied, including different concentrations of Arg-Leu-Pro and dGTP of the system. The data results showed that with the increase of Arg-Leu-Pro concentration, the system was hyperchromism effect on the UV spectra and red shift; with the increase of dGTP concentration, the Arg-Leu-Pro-DNA system was hyperchromism effect on the UV spectra, the DNA-EB system had significant quenching of the fluorescence spectrum, the maximum emission peak had blue shift and was static quenching. The binding constant K of Arg-Leu-Pro-DNA system obtained from the fluorescence spectroscopy data was 2.35×(10)³ L·mol^-1., the increasing of the viscosity. The results showed that the existence of the embedded mode.With the increase of His-Arg-Arg-Cys and dGTP concentration, the systems were hyperchromism effect on the UV spectra. The DNA-EB system has significant quenching of the fluorescence spectrum. According to the classical theory of fluorescence quenching, HRRC on the DNA-EB fluorescence quenching is not a simple static or dynamic quenching, but the two models co-exist, the binding constant K of Arg-Leu-Pro-DNA system obtained from the fluorescence spectroscopy data was 3.62×(10)⁴ L·mol-1, the decreasing of the viscosity. The results showed the existence of the two models for embedded and electrostatic.It was found that the mode of the interaction between Lys-Lys-Arg-Lys-Val-Cys and DNA was the embedded, the binding constant K of Lys-Lys-Arg-Lys-Val-Cys -DNA system obtained from the fluorescence spectroscopy data was 3.76×(10)⁵ L·mol^-1. It was found that the mode of the interaction between Ala-Ala-Ala-Ala-His-His-Ala-Cys and DNA was the two models for embedded and electrostatic, the binding constant K of AAAAHHAC -DNA system obtained from the fluorescence spectroscopy data was 4.36×(10)⁷ L·mol^-1, which showed it has strong interaction with DNA. So the initial guess, the longer the peptide chain and the more interaction strength with DNA.