Research progress of bioinorganic chemistry
Abstract: This paper mainly introduces the research progress of bioinorganic chemistry. Mainly from the study on the mutation, structure and properties of protein containing trace elements; Simulation of enzymes; Inorganic medicinal chemistry; This paper introduces the progress of bio-inorganic chemistry from four aspects, such as the study of metal element poisoning.
Key words: bioinorganic chemistry; Protein; Chelating agent; Enzyme; inorganic pharmaceutical chemistry
China Library Classification Number: O62 Document Identification Number: A
Article number:1009-0118 (2012) 07-0207-02.
Bio-inorganic chemistry is an interdisciplinary field of inorganic chemistry and biochemistry. Its task is to study the interaction between metals and biological ligands, which depends on the development of inorganic chemistry and biochemistry. Due to the progress of research methods, it is possible to reveal the bio-inorganic chemistry in the process of life. Bioinorganic chemistry is mainly divided into two parts: one is to study the function of trace elements in the object itself, and the other is to study the influence of external trace elements on the body.
Firstly, the function of trace elements in the object itself is studied.
(a) Study on protein containing trace elements.
Protein containing trace elements is the research object in bio-inorganic chemistry, which mainly relies on biochemical technology. Protein containing trace elements is a complex formed by trace elements and protein. Unlike enzymes, protein containing trace elements does not show catalytic activity, but it has other important functions. The current research is to find new protein and determine their structures and properties.
At present, the most popular protein is selenoprotein, because selenoprotein is the main form of selenium in the body and plays its biological function. The effects of selenium are mainly in cancer, neurodegenerative diseases and viruses, but the conclusions are not uniform. Now we are mainly exploring new selenoproteins as targets for preventive drug development, cancer treatment and drug screening. For example, Du Ming obtained a new selenium-containing protein from selenium-enriched Ganoderma lucidum by ammonium sulfate precipitation, and studied the relationship between its antioxidant activity and its selenium content. It was found that the antioxidant activity of the protein was related to its selenium content.
In addition, cytochrome has also been studied. For example, Guanmo Blue has studied the mutant of cytochrome b5. In order to deeply understand the influence of the 64th amino acid of cytochrome b5 on heme microenvironment and protein properties, the 64th amino acid residue of cytochrome b5 was mutated conservatively and non-conservatively. The results showed that the amino acid residue at position 64 of cytochrome b5 played an important role in stabilizing heme auxiliary group and maintaining the structure of protein, and the introduction of other amino acid residues at position 64 made the structure of protein unstable.
(B) the simulation of enzymes
The simulation of enzyme is to select the dominant factors from the enzyme and design and synthesize some non-protein molecules which can show biological functions and are much simpler than natural enzymes. By studying them, we can simulate the catalytic process of enzymes, find out the factors that control the biochemical process and get better catalysts.
For example, the study of selenase. By simulating the structure and function of selenase, people can not only understand the relationship between the structure and function of selenase, but also further develop drugs related to selenase. There are three main synthetic methods of selenases, one is chemical simulation of selenases, the other is chemical modification of selenases, and the third is genetic engineering to produce selenases. The chemical simulation of Selenase mainly focuses on the simulation of Se-N interaction in catalytic triad, the active center of Selenase. In this respect, there are mainly the synthesis of selenium enzyme mimics containing Se-N bonds and the introduction of nitrogen atoms near Se atoms to indirectly form intramolecular chelates through intramolecular chelation to achieve the effect of Se-N bonds. The main aspects of chemical modification of selenocases are: 1, transforming natural enzymes into selenocases; 2. Design selenium-containing biological imprinting enzyme; 3. Design selenium-containing antibody enzyme. Selenoprotein mimics play a very important role in understanding the biochemical functions of selenases. Selenoprotein mimetics have therapeutic potential in antioxidant, anticancer and antiviral activities.
Another example is Liu Haiyang's chemical simulation of nuclease. The chemical simulation of nuclease is of great significance to the research of biotechnology and molecular biology. Carole is a kind of macrocyclic compound with * * * yoke electronic structure, which makes its coordination chemical behavior easy to form complexes with metals, and the complexes formed by it have catalytic activity in many reactions. The research team studied the catalytic oxidative cracking of DNA by monohydroxy carbaryl manganese complex. The results showed that manganese complexes could catalyze the oxidative cracking of DNA, and the degree of cracking increased with the increase of reaction time. Song Yumin and others have studied the cleavage and bonding of DNA by yttrium complex of all-trans retinoic acid. Experiments show that the complex can cut plasmid DNA more effectively than ligands and metal ions under physiological conditions. Yue Lei et al. studied the DNA cleavage activity of chromium complex. The results showed that the chromium complex [Cr(bzimpy)2]+ had the activity of oxidative cleavage of DNA in the presence of H2O2, but the cleaved DNA could be repaired by Escherichia coli. ..
There are many reports about the simulation of nitrogenase. The purpose of simulating nitrogenase is to convert nitrogen molecules in the air into organic compounds under mild conditions, so as to make use of them. The simulation of nitrogenase activity centers is mainly molybdenum, iron and sulfur clusters, and there are also research reports on molybdenum mercaptan.
Second, study the influence of external trace elements on the body.
(1) inorganic medicinal chemistry
The development of inorganic drugs plays an important role in the field of bioinorganic. The discovery of anti-tumor effect of cisplatin has opened up a new field of inorganic medicinal chemistry. In the application of anticancer drugs, cisplatin drugs are still used in clinic at present, mainly including four platinum complexes of cisplatin, carboplatin, cisplatin and oxaliplatin. Since 1980 discovered the anticancer activity of dialkyl tin derivatives, people have successively synthesized dialkyl tin dihalides with cisplatin structure, organotin compounds with carboplatin structure, organotin carboxylic acid derivatives and so on. Germanium compounds, from the discovery of 197 1 synthesis? Because carboxyethyl germanium sesquioxide has anticancer activity, many organogermanium compounds have been synthesized one after another. There are also titanocene derivatives and rare earth complexes. Because cancer is the most important killer of human health and longevity, there will be great development prospects in the research and development of anticancer drugs. In addition to synthesizing new drugs, it is also the future research direction to improve the original drugs on the basis of the original drugs, because the original drugs have high toxic and side effects and small anti-cancer scope. Therefore, in the aspect of inorganic anticancer drugs, the main development direction is to synthesize anticancer drugs with broad-spectrum and high-efficiency anticancer activity, low toxic and side effects and long duration; In addition, there is no unified theory about the anticancer mechanism of inorganic metal drugs, so studying the mechanism of inorganic anticancer drugs is also the main research direction.
Inorganic drugs also have important applications in other fields. For example, the application of gold complex in anti-rheumatoid, and the application of gold thiol in the treatment of rheumatoid arthritis. In the process of treating stomach diseases, aluminum salts are also the main drugs, and bismuth-containing compounds are the main drugs for treating gastric ulcers. In the study of inorganic drugs, the therapeutic mechanism of various drugs on body diseases is still unclear, so the study of the mechanism of inorganic drugs has great prospects.
The development of radiopharmaceuticals is also the development direction of inorganic drugs. Due to the application of radioactive tracer and nuclear magnetic resonance in medicine, various contrast agents have become an indispensable aspect of doctors' clinical application, and barium is one of them.
(2) Treatment of metal element poisoning
When the external metal elements exceed the required concentration of the body, it will have a negative impact on the body and cause diseases. The toxicity of elements is mainly due to its strong coordination with biological groups. The treatment of metal element poisoning is mainly to study the chelating agent with stronger chelating ability, so that it can combine with toxic metal ions to form a more stable complex, and then excrete it. The ideal chelating agent must meet the following conditions: 1, water-soluble, and have sufficient chelating ability under physiological pH conditions; 2. The molecular size and structure must be appropriate; 3. Metal elements must be combined exclusively and quickly; 4, easy to be excreted; 5. No obvious toxicity. If EDTA is used to discharge excess ions, although EDTA has strong chelation, its selectivity is not strong. While discharging harmful metal ions, some beneficial ions will also be lost. For example, deferoxamine B is used to remove excess iron, but it cannot remove iron from heme or transferrin. At present, the research direction of medical chelating agents is mainly to study new drugs, because the current chelating agents can not meet the medical needs in terms of both types and the efficiency of discharging metal poisoning.
Third, the development trend of bio-inorganic chemistry
The future development trend of bio-inorganic chemistry is the organic close combination of life science and technology.
To study the principle of protein molecule and its biological function. There are only tens of thousands of human genes, but there are hundreds of thousands in protein, so the complexity of life needs to be explained from protein. At present, about 1/3 of the known protein enzymes need metal ions as cofactors, so it is very important to understand the structure and biological functions of these biomacromolecules. The study of nucleic acids. It is a main focus of bioinorganic chemistry to study the selective recognition and regulation of metal elements on nucleic acid sequence, configuration and region. For example, many zinc lipoproteins have been found to regulate DNA or RNA. This research will have an important impact on future inorganic drugs.
As life science will be one of the research hotspots in 2 1 century, bio-inorganic chemistry closely related to life science will be greatly developed and will make greater contributions to mankind.
References:
[1] hong maochun, Chen Rong, Liang wenping.265438+20th century inorganic chemistry [M]. Beijing science press, 2005.
Kang et al. Advanced inorganic chemistry [M]. Shanghai: East China University of Science and Technology Press, 2007.
This is Feng Jiao. Inorganic chemistry [M]. Beijing: Science Press, 2006.
Sun yinwei Coordination chemistry [M]. Beijing: Chemical Industry Press, 2004.
Qu Ping, He Hua, Liu Xuhui. Antitumor activity and mechanism of rhodium complex [J]. Chemical Bulletin, 1999, (12):1-1.
Liu Haiyang, Liu Lanying, Zhang Lei. Oxidative cleavage of DNA catalyzed by manganese (Ⅲ) crown ether complex [J]. Journal of Chemistry of China University, 2007, (9): 1628- 1630.
Song Yumin, Song Xiaoli, Luan Nina. All-trans yttrium (Ⅲ) retinoic acid complexes cleave and bind DNA [J]. Journal of Inorganic Chemistry, 2005, (11):161-kloc-0/6668.
Yang Pin. Development of Bioinorganic Chemistry in China [J]. Chemical Bulletin, 1999, (12):1-1.
Huang Kaixun, Liu Qiong, Xu. Study on antioxidation of selenoprotein and discovery of amino acid 2 1 [J]. Journal of Inorganic Chemistry, 2008, (8):1213-1218.
[10] Nie Jing, Han Meijiao, Wang Kezhi. [Ru(phen)2dppz]2+ dimerization and its influence on DNA bonding properties [J]. Journal of China University Chemistry, 2007, (10):1833-1835.
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