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Study On The Interaction Between Biochemically Active Molecule And DNA

Posted on:2006-01-12Degree:MasterType:Thesis
Country:ChinaCandidate:H X WuFull Text:PDF
GTID:2121360152990052Subject:Analytical Chemistry
Abstract/Summary:PDF Full Text Request
DNA is the carrier of genetic information and plays an especially important role in the course of genetic. Investigation of DNA is important in the life sciences field. DNA is the main target molecule that exists in anticancer and antiviral therapies. All cell and virus carry DNA. Normal heredity function of DNA depends on the physical and chemical interaction of other molecules with DNA.Interaction of DNA with small molecules, especially drug molecules affected physiological and physical chemical character of DNA and changed the transfer and copy of DNA. Hence it is meaning that interactions of small molecules with DNA are investigated to understand bind of DNA with protein, anticancer mechanism and to design and synthesize new drug。 In medicament, it possible to foresee major steps forward in our understanding of the molecular basis Of disease, both from attack by external pathogens and internally from variations within the human genome resulting in a plethora of new molecular therapeutic targets for drug design and discovery.A variety of techniques from molecular biology have been used in research laboratories to study the effects of DNA binding small molecules, such as the gel mobility shift assay, ~1H NMR, DNA foot-printing assay, and fluorescence-based assays, UV-Vis spectrum and viscometry.Based on the above view, in this paper we first provide a general introduction and conclusion of the research about the interaction of molecule that is active in life-form with DNA; secondly, we synthesized a new water-soluble porphyrin meso-tetrakis{[4-(1-pyridyl)propoxy]phenyl}porphyrin (IPPBr) and its Ni complex(TPPBr(Ni)), Zn complex(TPPBr(Zn)) and characterized these porphyrin by UV-Yis spectra, ~1H NMR ,and infrared spectra; thirdly, we studied the interaction of these porphyrins with calf thymus DNA (CT DNA) by UV-visible, fluorescence and circular dichroic spectroscopy and viscosity measurements; fourthly, we studied the interaction of methylene blue(MB) with CT DNA by UV-visible spectroscopy, viscosity measurements, electrochemistry; fifthly, the poly(mcthylene blue)-modified glass carbon electrode's electrochemical behaviour was investigated by cyclic voltammetry (CV) and SECM experiments.Part I General Introduction and ConclusionIn this part, the development in the studies of DNA, including sturcture of DNA, interaction of DNA with other matter and the mothods about interaction of DNA and small molecule. It is important to study DNA interaction with drug in theory and in practice. Reports about the action of the porphyrin that alkyl connected N-position with DNA are very few in the word. And we study action of methylene blue with DNA solution by mainly electrochemical methods.Part II Synthesis of a novel water-soluble porphyrinA new water-soluble porphyrin meso-tetrakis{[4-(l-pyridyl)propoxy] phenyl} porphyrin (TPPBr) and its Ni complex(TPPBr(Ni)), Zn complex(TPPBr(Zn) have been synthesized and characterized by UV-Vis spectra, ~1H NMR, and Infrared spectra.Part III Study on the Interaction of water-soluble porphyrin withDNAA new porphyrin meso-tetrakis{[4-(1-pyridyl)propoxy3phenyl}porphyrin (TPPBr) and its Ni complex(TPPBr(Ni)), Zn complex (TPPBr(Zn))have been synthesized. The interaction of these porphyrins with calf thymus DNA (CT DNA) has been explored by UV-visible, fluorescence and circular dichroic spectroscopy and viscosity measurements. The results suggest that these porphyrins can bind to DNA by the same binding mode. TPPBr outside binds by self-stack with DNA both at low drug load r (s=[porphyrin]/[DNA]) and high drug toad. Though TPPBr(Ni) and TPPBr(Zn) have center metal, binding mode with DNA has little difference compared with TPPBr, dominating out-binding mode with different direction along DNA. The binding constants of the TPPBr, TPPBr(Ni) and TPPBr(Zn) to DNA were 4.65 × 10~5M-1, 3.2 ×10 ~5 M-1 and 2.64 × 10~5M-1, respectively. A colored precipitate was found after time in the porphyrin's viscosity measurement. The reasonable interpretation is the porphyrins with alkyl connected N-position of p...
Keywords/Search Tags:DNA, porphyrin, methylene blue, interaction
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