"I am sulfur element acting character! "I am sulfur element acting character!!
Write civil | Jiang Xuefeng
Sulfur distributings in nature wider: In the universe, sulfur element content is ranked the 10th, content is about 0.002% ; In the lithosphere, the abundance content of sulfur is ranked the seventeenth, content is about 0.048% (press quality plan) ; In human body, sulfur element contains sulfur to be about 0.25% , after row oxygen, carbon, hydrogen, nitrogen, calcic, phosphor, Potassium, rank the 8th (graph 1) [1] . These data seem tell us, or reflected the life assemble of sulfur element magical life dependency.
Graph 1. The nature of sulfur distributings
Contain sulfur life element
In making protein amino acid, acid of half Guang ammonia and acid of armour sulfur ammonia contain sulfur element. Peptide of cereal Guang pleasant is almost body of consist in mankind the peptide of the few that contain sulfur in each cell, it is mix by acid of ammonia of glutamic acid, half Guang pleasant ammonia acerbity condensation and into. The Qiu that because its contain,returns GSH of peptide of pleasant of archetypal cereal Guang base (- SH) , make its are had exceed strong cleared put oneself in another's position inside the ability of freedom radical, the cell inside protective system is not oxidized to injure, defer consenescence and fight exhaustion, it is the important hero that fights cancer even.
Airframe produces overmuch freedom in metabolic process base can injure biomembrane, invade life macromolecule, accelerate airframe consenescence, cause tumor or sclerosis of arterial congee appearance, the element that contain sulfur provides reductive atmosphere inside human body, one of its main physiology action offer a kind of important antioxidant inside body namely, prevent overmuch freedom base to the body damage. Be elements of these important the life that contain sulfur, the indispensable part in constituting life (graph 2) .
Graph 2. The sulfide in life style
The sulfur structure that needs to one kind calls 2 sulfur key in protein 2 level structure is participated in [2-5] , 2 sulfur bolt the formation in protein has very crucial effect in the process: Above all, the formation that 2 sulfur bolt makes the dimensional structure of protein peptide catenary compact and stereo and concentrated, thick; In the meantime, when its by reductive after becoming Qiu radical, can make protein structure temporary " untie a person " , the function is changed related implementation, heredity is duplicate; Oxidize afresh, 2 sulfur key is met again according to former conjugate reset " build the bridge " , this is famous through forming 2 sulfur key compose builds protein the process of structure of 23 class fold.
Realize artificial complex first by our country scientist bovine insulin, it is one owns the B chain that the A catenary of 21 amino acerbity composition owns 30 amino acerbity composition with another, element of a when join through catenary of two pairs of 2 sulfur and become double catenary, and A catenary oneself still has a pair " lock " 2 sulfur bolt (graph 3 on) .
20 centuries 50 time, protein is the heat that world biochemistry domain studies. 1955 British scientist F. Mulberry rules and forms of classical poetic composition determined first all and amino acerbity alignment of bovine insulin, also obtained accordingly Nobel is chemical 1958 award. But suffer be confined to the condition at that time, think implementation composes the issue that is special difficulty artificially.
In August 1958, fasten 3 units to undertake study jointly by biology of institute of institute of biochemistry of Shanghai of the Chinese Academy of Sciences, organic chemistry of Shanghai of the Chinese Academy of Sciences, Beijing University, at first the finishing deadline of set is 20 years, need to prove the special time of Chinese actual strength in that earnestly however, the scientists that participate in a project expect to be able to shorten date for 5 years.
China synthesizes the experience of the respect without any protein at that time, had not made the amino acid of any forms even, prep let alone compares the polypeptide synthesis with amino more complex acid, everything is from 0 begin, feeling stone to cross a river. 17 kinds of of insulin form a complete set amino acid, need an import, before one year when begin in the project however, russia aid China the expert is mogged, in revive the relation moves toward freezing point, and Euramerican in those days offer sale absolutely impossibly also to synthesize the amino acid that bovine insulin needs. In those days scientists built the factory building that synthesizes amino acid technically with one's own hands with the time of a few months, assure to study the supply of amino acid in the process.
The compose that another enormous challenge is 2 sulfur key is built, because of the A in bovine insulin, b catenary recombines means to have boundless kind. Hypothesis ideal has an A only in condition solution, b catenary, 2 sulfur key is formed to 15 is plant between acid of half Guang ammonia likelihood. And the A in real solution, b catenary amount is rife, the join means that 2 sulfur bolt can show exponential level growth, because this combines correct probability,be boundless actually 1/0. Fumble through a year of much effort however, they found a group of conditions, make correct join A, the probability of B catenary rose 10% . Realized the synthesis of artificial ox insulin finally first in September 1965. In November 1965, achievement of this one important research is in with brief form above all " Chinese science " publish, and in April 1966 full text is published.
Graph 3. Insulin structure
Person insulin and sex of bovine insulin likeness are taller, there just is little difference on the structure: The molecular structure of person insulin (pursue 3 times) only 3 amino acid and bovine insulin are different.
20 centuries 90 time later period, after people is undertaking got-up to person insulin structure, gotten insulin kind medicaments can make insulin fits need of human body physiology more. This kinds of medicaments is imitate of insulin of normal human body secrete, compound an as similar as person insulin on the structure matter thereby. Insulin kind medicaments and person insulin are compared, have effect faster, it is normal to can help more accurate imitate the insulin metabolization course that the person leaves in physiology condition, can better control blood sugar.
Contain sulfur remedy
Sulfur is used extensively also at contemporary medicaments structure in the center, the important composition that is medicaments structure is unit. For example, in peptide kind in medicaments, had used sulfur key is slow the process that releases sulfur alcohol achieves medicaments slow the result that release, the medical effect time that increases medicaments thereby and availability [6] .
The sulfur sulfur key in sulfur structure still can serve as " link bridge " apply extensively at fighting medicaments of body idol couplet (Antibody-drug Conjugates, ADC) in. After because ADC medicaments is to be based on power,powerful young member medicaments enters tumor cell " link bridge " S-S key ruptures to just begin to release, can enhance the security of medicaments significantly not only consequently, reduce poisonous side effect substantially, and can enhance effectiveness greatly, curative effect outclass is the same as the antibody of common odd clone of drone, the delegate that is direction of development of odd clone antibody and forward position of young member medicaments (graph 4) [7] .
Graph 4. Contain sulfur ADC remedy
As a result of technical reason, first ADC medicaments just appears on the market formally till 2000. The ADC remedy that is approved by FDA at present is only also 4, basically use at the cure of cancer of of all kinds blood and hypostatic tumour.
The model of medicaments of generation ADC is represented even if the auspicious appropriate sheet of development of brightness luck company is fought (Mylotarg) , its structure contains important sulfur sulfur key to regard a link as body. Of this medicine appear on the market process it may be said 3 fold, the ADC medicaments horizontal stroke that it appears on the market at serving as first approval 2000 comes out for nothing use at treating leukaemia of sex of acute marrow cell, be in however more large-scale 3 period clinical trial discovers this medicine appears the problem such as premature degradation, be forced to retreated city 2010, but was appeared on the market by new approval again 2017.
Sheet fights the Qu Tuozhu that the typical delegate of medicaments of the 2nd acting ADC is development of collect family name (Kadcyla) , sulfur element is contained likewise in its structure. This medicaments was approved to be used at the cure of patient of HER2 electropositive breast cancer by FDA 2013. Opposite at medicaments of generation ADC, qu Tuozhu sheet is fought have in the stability in haemal circulation tall, be able to bear or endure suffer a gender good, improved the advantage such as remedial index.
ADC medicaments research and development develops in Euramerican country not only rapid, also advancing quickly in China, the achievement of heavyweight research and development that theres is no lack of to have ADC remedy in succession like the company such as constant luck medicine, Qi Lu medicine among them appears.
Graph 5. Contain sulfur to appear on the market ADC medicaments
Contain sulfur antibiotic
Sulfur element is having more a long time ago history in the application of antibiotic domain. Penicillin kind medicaments is the mankind discover the earliest fight fungus medicaments, penicillin (penicillin) with Amoxilin the model that is this kinds of medicaments is represented.
The discovery of penicillin is an accidental opportunity actually: During the the First World War, england is royal · of Alexander of header of army medical team Fulaiming casual all germiculture base caboodle of a head was in on the couch of lab corner. Result, his discovery is fostered among them base was polluted by mould carelessly, all round mould the grape coccus of circuit was killed. Major researcher is met an unusual education base desertion, only Fulaiming generated strong interest to this, then he extracted the mould in education radical cautiously, them rarefied education rises, discovering these compound is penicillin actually. From now on, penicillin is used as antibacterial content, its development enhanced the ability that the mankind resists bacterial sex appeal is caught successfully greatly, drove the birth with familial antibiotic [8] .
But penicillin kind its resist antibiotic bacterium chart is narrower, basically be opposite bacterium of positive of change orchid family name is effective. The Amoxilin that develops subsequently is penicillin of a kind of half synthesis kind wide chart antibiotic. General application received since entering the market 1972, sales volume of drug of completely beautiful 2011 prescription ranks the 20th [9] . The head Bao that develops subsequently kind antibiotic has the music that fight bacterium the wide, action that fight bacterium is strong, be able to bear or endure penicillin is enzymatic, allergic reaction relatively penicillin kind wait for an advantage less.
Head Bao kind antibacterial invents time to be mixed early or late by its the different cent of the function that fight bacterium is one, 2, 3, 4 generation [10] . Element of bacterium of Bao of generation head begins to appear on the market at the beginning of 60 time. From the function that fight bacterium for, the element of head Bao bacterium of different breed can have the respective characteristic that fight bacterium, if head Bao thiophene is right change orchid is electropositive the action fighting bacterium of bacterium relatively actor, zun forest is opposite a Bao bacterium of sex of certain change Lan Yin has certain effect. But, element of bacterium of Bao of generation head is electronegative to change orchid the β of bacterium - inside the resistance with acyl enzymatic amine is weaker, accordingly, bacterium of change orchid negative is right this acting antibiotic is able to bear or endure more easily medicine.
Element of bacterium of Bao of head of the 2nd generation is positive to change orchid the efficiency fighting bacterium of bacterium and generation close or inferior, and the action of electronegative to change orchid bacterium is relatively exceedingly good, expression is fight enzymatic function strong, the chart that fight bacterium is wide, be out of shape to positive of indole of bacterium of Nai a twenty-five-stringed plucked instrument, part acerbity bacili of citron of bacillus, part, partial bowel bacili is belonged to all have the effect that fight bacterium.
Element of bacterium of Bao of head of the 3rd generation is positive to change orchid the efficiency fighting bacterium of bacterium is general under generation, the action of electronegative to change orchid bacterium relatively element of bacterium of Bao of head of the 2nd generation is more advantageous. The chart fighting bacterium of element of bacterium of Bao of head of the 3rd generation expands somewhat again than the 2nd generation, be able to bear or endure enzymatic performance is strong. Be able to bear or endure to generation or element of bacterium of Bao of head of the 2nd generation a few change orchid of medicine are electronegative bacterium individual plant, usually of bacterium of Bao of head of the 3rd generation but effective. cannot use at controlling coccus of golden yellow grape to affect.
Discover a few new breed are like oxime of head Bao Bi subsequently (Cefepime) etc, have the property fighting bacterium of element of bacterium of Bao of head of the 3rd generation not only, still have the effect that fight bacterium to grape coccus, call element of bacterium of Bao of head of the 4th generation. Xi of carbolic green mildew kind antibiotic is the chart that fight bacterium the widest, the SARS with the strongest active that fight bacterium β - inside acyl amine antibiotic, because its have pair of β - inside acyl amine enzymatic stability and noxiousness are low characteristic, had become treatment one of antibacterial thing with serious bacterium the mainest infection (graph 6) .
Although the antibiotic of all sorts of types is developed ceaselessly, but still appeared of late the super bacterium that myrrh can control. Gene mutation is the prime cause that produces super bacterium. The bacterium is able to bear or endure the generation of property of a medicine is clinical the result that goes up to apply antibiotic extensively, and the abuse of antibiotic accelerated this one process. Accordingly, people should prevent the abuse of antibiotic as far as possible in daily life, medical practicable corner is not had when preventing to need to use antibiotic truly.
Graph 6. Contain sulfur antibiotic remedy
Sulfur, it is element of a kind of life, its valence condition diversity mixes ascribe compose diversity, its return the electron that is it to discharge cloth and dimensional orbit constitutionally. Develop as the alternate confluence of different course, the magical quality of sulfur element will receive further progress and application in life chemistry, sulfur element hopeful acts more and more important role in life.
Author brief introduction
Jiang Xuefeng, was born in Gansu Province Lanzhou in December 1980, currently hold the post ofchemistry of Hua Dong Normal University and professor of molecular project college, doctoral student adviser. He is applied " from inorganic sulfur to organic sulfur " changed concept, compose built distinctive green vulcanization to learn a system. July 2018, international is dinkum as chemical as application federation (IUPAC) the chemistry of the 25th international that holds in Australia teachs the conference to go up, professor Jiang Xuefeng is chosen to be " spokesman of element of sulfur of periodic chart of global youth chemist " .
Reference material
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[5] Wang, m. ; Jiang, x. Top. Curr. Chem. 2018, 376, 14.
[6] Zhao, j. ; Jiang, x. Chinese Chem. Lett. 2018, 29, 1079.
[7] Senter, p. D. Curr. Opini. Chem. Biol. 2009, 13, 235.
[8] Bruggink, a. β of Synthesis Of - Lactam Antibiotics. Springer. 2001, p. 17.
[9] Elizabeth, a. ; Vitaku, i. E. ; Njardarson. J. T. J. Med. Chem. , 2014, 57, 2832.
[10] Feng, m. ; Tang, b. ; Liang, s. ; Jiang, x. Curr. Top. Med. Chem. 2016, 16, 1200.
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