Into Unscientific

  Chapter 611 Targeted drugs launched!

   "Native donkey?"

  In the ward.

  Heard the word that came out of Xu Yun's mouth.

  Old Guo, who was sitting upright in his seat, suddenly showed a look that was so true.

   It really is a donkey.

  In the capital, Xu Yun was squeezed like a donkey, and Xu Yun was squeezed like a donkey. Why do you feel a little happy?

   Then he paused, pulled his mind back to reality, and asked Xu Yun again:

   "Xiao Han, it's true that donkey cells are easier to obtain than human cells, but can this thing really detect DNA differences?"

  “.Could it be that you usually complain about eating too much donkey hair, so you want to get revenge?”

   At the end, Lao Guo had a strange expression on his face.

  Xu Yun has often persecuted the local donkeys in the base in the past few days. The most representative one is the donkey pulp film produced by the previous "Xianxian Sword" project.

  As far as Lao Guo knows, the hundreds of donkeys in the base can’t even make up twenty hairs

   But opposite him, Xu Yun seriously shook his head and explained:

   "Guo Gong, I didn't lie to you, the genes of local donkeys are really different from foreign donkeys."

   "Otherwise, why can the apocrine secretion of our local donkeys produce that kind of film, but foreign donkeys can't?"

  Xu Yun really didn't intend to take revenge this time.

  When referring to the expansion and cultivation of Yi'an bacteria, Xu Yun and his good friend Qiu Sheng once talked about two papers.

   That is 10.13881/j.cnki.hljxmsy.2021.02.0100 and 10.28502/n.cnki.nkjrb.2014.007254.

  The subject of the dissertation took place in 2014.

   At that time, led by Huaxia Gene Bank, academician Yang Huanming of the Chinese Academy of Sciences once organized a gene sequencing of donkeys, which was also the world's first large-scale donkey genome project.

   During the subsequent detection process, the detection team once discovered many very strange situations.

  For example.

  Native donkeys will produce a small amount of calcium thioglycolate in their bodies, which is an ingredient in hair loss agents.

  For another example, they found that in native donkeys, there will be a LightPoint phenotype, referred to as LP phenotype.

   Under this phenotype.

  Mutants of the MC1R gene not only affect the hair, but also affect the amplification of the CDS sequence of the PepT1 gene.

  This directly leads to a very strange ratio of Young's modulus of elasticity in donkey hair, and it is quite obvious.

  For example, when the relative humidity increases from 0 to 100%, the axial swelling of donkey hair is only 1%.

  The ratio of Young's modulus to shear modulus is reduced from 217:1 to 15:1.

   In addition,

  A pentose phosphate pathway product with 225 differential metabolites from the high tenderness group was also detected in the hair of native donkeys. The results of this study were also published in the sub-journal of Nature.

   Therefore, these phenotypes can be used as test points in the DNA sequencing process.

   In a sense.

  Native donkeys and foreign donkeys are even easier to detect this phenotype than normal people and tumors.

  “.”

  After hearing what Xu Yun said.

  The expression on Lao Guo's face also became hesitant.

   seems

   Really makes sense?

  After all, in order to ensure the "exclusive agency" of the donkey pulp film, the rabbits have indeed experimented with various types of foreign donkeys.

   Such as Pakistani donkeys, Neon donkeys, Egyptian donkeys, etc.

  But after rounds of experiments, it is true that only local donkeys can produce the donkey pulp film that meets the requirements—otherwise, the rabbits would not have the confidence to trade it.

  If it is explained from the genetic point of view, it seems that it can indeed be explained?

   Then he pondered for a moment, decided to put the matter aside, and looked at Xu Yun again:

   "Xiao Han, since the problem of DNA testing can be solved with a local donkey, then you can finish the rest of the things you need."

   "If the conditions and equipment at the base meet the requirements, then we will start researching immediately. If there is still something missing, then contact the capital as soon as possible to supplement it."

  Xu Yun hummed immediately when he heard the words, thought for a moment, and explained:

  "In addition to the structure and target, the rest of the targeted drug is the enzymes and reagents in each link, which involves more chemical steps."

   "After all, if the drug and the target are to be combined, some specific enzymes must be required for recognition and combination. There is also a DNA polymerase that is required for PCR technology to complete the amplification."

  Xu Yun finished speaking.

  Lao Guo nodded, expressing his understanding.

  Although he has never been exposed to the concept of targeted drugs before, he still knows about enzymes.

  The discovery of enzymes can be traced back to 1897, when the German chemist Buschner extracted the brewing enzymes that can ferment alcohol from ground yeast cells.

From then on.

  The concept of enzymes has entered the field of vision of biology.

   Then in 1930.

  Across the sea, biochemist Northrup and others isolated and purified pepsin, proving that the essence of the enzyme is protein.

   Follow the normal historical trajectory.

   In three years, Northrup will be awarded the Nobel Prize for this discovery.

  Nowadays, the enzyme production technology in the chemical industry has developed to a level that is barely self-contained, even in China.

  So when Lao Guo heard Xu Yun mention the targeted enzyme, he quickly followed his rhythm.

   Then Xu Yun paused, and then raised an index finger:

   "First of all, let's talk about the enzymes needed for PCR. In fact, there is already a precedent for the extraction of this enzyme in Europe, mainly from Escherichia coli."

   "The enzyme can be obtained by culturing, centrifuging and extracting Escherichia coli."

   Well known.

  The basic principle of PCR technology is through the complementary pairing of primers and DNA template strands.

  Then use enzyme catalysis in the PCR reaction system to amplify the template DNA to a specified multiple.

  The first step of the PCR reaction is to separate the double-stranded DNA into two single strands, and then pair the two ends of the DNA through primers to form a starting structure of double-stranded DNA.

  Next.

  Auxiliary enzymes start to synthesize DNA strands downward on the initial structure of double-stranded DNA through DNA polymerization.

  Taq enzyme is commonly used in later generations. It is extracted from Thermus aquaticus, and its protein has a strong ability to resist high temperature.

But on the other hand.

  Its extraction technology requirements are very high, and a relatively complete extraction process will not appear until the end of the 1980s.

   Coincidentally.

  In his previous life, when Xu Yun was writing a novel called "The Empire of Science and Technology Starts from Local Donkeys", he happened to write about hand rubbing PCR technology.

   As a result, I met a reader at that time. Xu Yun hadn’t finished writing the plot yet, so he kept asking Taq enzyme how to solve it.

   This is very typical to speak from the perspective of God, because Xu Yun tmd didn’t plan to use Taq enzyme at all.

   Compared with Taq enzyme, Klenow enzyme isolated from E. coli can have the same effect.

   Actually.

  In the early days of PCR technology, Klenow enzyme was used.

  The extraction technology of this enzyme is very simple, as long as there is a centrifuge, the rest of the steps can be easily done.

   Compared with Taq enzyme, Klenow enzyme is not so resistant to high temperature and is prone to denaturation.

   That is to say, in the experiment, the enzyme needs to be added again in each cycle, which seriously hinders the popularization and promotion of PCR technology.

   But the problem is that Xu Yun does not intend to promote PCR technology immediately, what he needs is to use this technology to produce targeted drugs for Yang Kaiqu to treat diseases.

   It's like Xu Yun's hand rubbing generator in the Northern Song Dynasty copy.

  At that time, Xu Yun only needed to ensure that he could provide the electricity that could complete the electrolysis, and he didn’t want to rub his hands on a nuclear power plant.

  In the Northern Song Dynasty, Lao Su, a local rich man, distributed coins, but now Xu Yun is backed by a huge country.

  Although rabbits are still very poor these days, there is still some financial resources and ability to add Klenow enzyme to every cycle.

   "Extract enzymes from E. coli?"

  Old Guo Wenyan blinked and asked subconsciously:

   "Xiao Han, centrifugation in the field of microbiology should require high-precision instruments, right?"

   "It may not be a problem in Europe, but based on the current situation in our country, can we get it all together in a while?"

"sure."

  Xu Yun nodded very easily, without any frown, and explained confidently:

   "Guo Gong, although in terms of process, it requires a shaker and a high-precision filter membrane, it may indeed be difficult to find equipment with the same standard in China."

   "But on the other hand, although we don't have the same level of equipment, we have more sophisticated instruments than this."

   "A more sophisticated instrument?"

  Old Guo was slightly taken aback, unable to follow Xu Yun's train of thought for a while.

  But he is a top science and engineering expert after all, and centrifugation is also his proficiency direction, so he soon realized something:

   "You mean the centrifuges and the batch of gas diffusion membranes in Jincheng 504 Factory?"

Snapped!

  Xu Yun snapped his fingers again. Since his hands returned to normal, he suddenly fell in love with this action:

"bingo!"

   That's right.

   The extraction equipment that Xu Yun thought of was the centrifuge and gas diffusion membrane used to enrich uranium in Plant 504.

   After officially entering the core sequence of the base.

  Xu Yun was finally informed of the [truth] of the gas diffusion membrane—although he already knew about it

  This is a centrifuge for enriching uranium, much better than any shaker.

  The other gas diffusion membrane was only partially used in the Zhuxianjian project, and now there is still a thick stack in the warehouse of the 221 base.

   Having solved these two problems, the rest is much simpler.

  For example, the eluent required for Klenow enzyme can be prepared with methanol, isopropanol, and ammonium acetate. This technology has been mastered by rabbits during the production of tetracycline hydrochloride.

Of course.

  Although the growth environment of E. coli on the petri dish is actually very clean, the word does have some congenital smell.

  Therefore, if there is no accident, the ice cream business of Factory 504 may be affected in the future

   Then Xu Yun paused and continued:

   "In addition to the Klenow enzyme for PCR, there are two sources of targeted enzymes required for targeted drugs."

   "One is a synthetic metalloenzyme. I don't know the specific ingredients, but the efficiency is a little higher than the second one."

"The other is a natural enzyme, which comes from marine actinomycetes—although the place where the marine actinomycetes were found in that notebook is in the UK, as long as you spend a little time in the high latitude areas of the country, you should be able to find this kind of bacteria kind."

   "Both of these two enzymes can be used as recognition enzymes for targeted drugs. If these enzymes are added on the basis of the drug structure reference paclitaxel, the remaining problem is only clinical trials."

  Students who were cancer cells in their previous lives should know this.

  In the development of targeted drugs, metalloenzymes are a very common class of recognition enzymes.

  They use active site metal ions for catalysis, and more strictly speaking, active site metal ions of metalloenzymes need to form stable coordination with active site residues and participate in related chemical reactions.

  Metal ions usually act as Lewis acids or redox partners and promote catalytic reactions by increasing the ground-state energy of reaction partners, enhancing substrate binding, or stabilizing reaction intermediates.

  In the year 2023 that Xu Yun travels through.

  There are about 70 metalloenzyme small molecule inhibitors that have been officially approved for clinical use.

  Most of these inhibitors have a direct coordination interaction with the active site metal ion through a specific chemical type, which is usually called a metal-binding pharmacophore. It is the MBP that many people learn to die or live.

   Although Xu Yun did not give a specific formula for avoiding suspicion, there are only two metalloenzymes that can form a combination with the polyhydric structure of paclitaxel:

  Boron or zinc.

   Among them, boron Xu Yun reckons that domestic technology will not be able to make a breakthrough smoothly, so the final one with a high probability of being selected should be zinc.

  As for the second natural enzyme.

  Xu Yun said it was marine actinomycetes, but he was actually referring to marizomib, a cyclic peptide compound extracted from marine sponges.

  It is the first compound that can inhibit the combination of ubiquitin-conjugating enzyme UBC13 and UEV1A, and it can probably recognize and inhibit the growth of 60 tumor cell lines.

  In fact, there are quite a few places in China where marizomib can be extracted, basically at higher latitudes. Probably take Shanghai as the line, and you can find corresponding targets in the ocean above Shanghai.

  At the same time, in addition to marizomib, Flavopiridol that can be extracted in Sange is also a good choice.

  However, in this period, rabbits must develop in a low-key way, so Xu Yun finally gave up this idea.

Of course.

  In the development of targeted drugs, some Xu Yun can find a way to solve, and some need to bear the risk.

  For example, diagnostic kits for targeted drugs, which are tools used to detect people who benefit from drugs, involve nanotechnology and CTC, and Xu Yun is really helpless in this regard.

  At that time, he will at most use a specific antibody to do an enrichment test, and the accuracy will not exceed 80%.

   In other words.

  Even if the targeted drug is produced successfully, whether Yang Kaiqu can take it at that time and how effective it will be depends on his own physique.

   But what Xu Yun didn't know was.

   Far away in the Institute of Pharmacy of the Academy of Medical Sciences in the capital, he had already mastered a few small pills a long time ago.

  That is the fourth generation quinolone

  “.”

   After Xu Yun finished introducing the information.

  Old Guo glanced at Lin Yu subconsciously. Among the few people present, this one is a well-deserved expert in medicine:

   "Doctor Lin, what do you think?"

   Right now.

  Lin Yu's expression is still a little shocked.

  Although in the past period of time he had heard a lot about Xu Yun's half-familiar strange thing, this was the first time he had personally experienced it.

   As expected of the legendary Mr. Lying Deaf

   Fortunately, after all, he is also a big brother who has seen a lot of troubles, so he recovered quickly.

  I saw him pondering for a moment, and finally a flash of determination flashed in his eyes, and said:

   "Director Guo, I agree with Comrade Han Li's plan, you can give it a try!"

  Although what Xu Yun said was somewhat beyond his understanding, he couldn't find anything to refute or question the specific principles.

  In addition, Yang Kaiqu's body is already extremely bad. If he doesn't try, he will definitely not be able to survive. If he tries, there may be miracles.

   To put it bluntly, it is

  Dead horses are treated as live horse doctors.

   Then Lao Guo looked at Yang Kaiqu again, and said to the client:

   "Comrade Kaiqu, what do you think?"

  Yang Kaiqu’s answer was as open-minded and calm as ever:

   "Youlai, to tell you the truth, before coming to the base, I would definitely not agree to the country wasting these resources for me."

   "But now that I have obsessions, I'll have the audacity to enjoy the preferential treatment for a while."

   "Didn't Xiaohan just say that there will be some human clinical trials after the drug is ready? Don't look for other people or donkeys at that time, just experiment and observe on me."

   "If it works, I will try my best to live on. If it doesn't work or has any side effects, it can also serve as a reference for drug development."

   "Anyway, I have already written in my suicide note. After my death, my body will be donated to Southwest Medical University. The country has given me the treatment of a member of the academic department, but I have not made many years of contributions. I can only repay the country in this way."

  The scene was suddenly silent, and Xu Yun was filled with emotions.

  Yang Kaiqu in history also said the same, and even more so. In this era, there are indeed quite a few people who have a kind of sincerity and awareness that will move future generations.

   After about a minute.

  Li Jue opened his mouth to break the silence in the ward, and saw him solemnly addressing Yang Kai:

   "Okay, since you have no objection, Comrade Kaiqu, I will start drafting the report after I return to the office."

   "Comrade Kaiqu, believe me, you will definitely be able to see the scene of the atomic bomb explosion!"

  Yang Kaiqu laughed:

   "Since this is the case, then I will wait and see!"

   More than ten minutes later.

  Yang Kaiqu's strong body entered a sleepy state again, Li Jue and old Guo Xuyun took the initiative to leave.

  Afterwards, Li Jue brought Lao Guo and Xu Yun to the office of the factory, and sent someone to invite Liu Youcheng from the chemical laboratory, and began to draw up the relevant report content.

   Two hours later.

  A telegram was transmitted to the capital.

   Another hour passed.

  A reply came from the capital:

  【Agreed in principle to the targeted drug preparation plan, and the relevant equipment and personnel will arrive at the base in the near future】.

  Targeted drug development plan.

   Now let’s start!

Note:

  I didn’t update yesterday, because I drove to a laboratory to observe the reproduction of room temperature superconductivity, which is the synthesis route of the rod. I won’t talk about the specific laboratory. I will try to see if I can make a video or something.

  (end of this chapter)