Lao Guo, who was sitting in his seat, suddenly showed a look that was indeed true.
It really is a donkey...
In the capital, Xu Yun was being exploited like a donkey, and Xu Yun was exploiting a donkey like a donkey. How come I feel a little happy...
Then he paused, brought his mind back to reality, and asked Xu Yun:
"Xiao Han, it is true that local donkey cells are easier to obtain than human cells, but can this thing really detect DNA differences?"
"...Could it be that you usually have complaints about eating too much donkey hair, so you want to go back for revenge?"
At the end of the sentence, Lao Guo's expression was slightly strange.
Xu Yun has frequently persecuted the local donkeys in the base in the past few days. A very representative example is the donkey pulp film produced by the previous "Zhu Xian Sword" project.
As far as Lao Guo knows, the hundreds of donkeys in the base now can't even make 20 hairs...
But opposite him, Xu Yun shook his head seriously and explained:
"Guo Gong, I'm not lying to you. The genes of local donkeys are really different from those of foreign donkeys."
"Otherwise, why can the apical secretions of our local donkeys be able to produce that kind of film, but not foreign donkeys?"
Xu Yun really didn't intend to retaliate this time.
When the amplification culture of Yi'an bacteria was mentioned, Xu Yun and his good friend Qiu Sheng discussed two papers.
That is, 10./j.ki.hljxmsy.2021.02.0100 and 10./n.kjrb.2014.007254.
The topic of the thesis occurred in 2014.
At that time, led by the China 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 inspection process, the inspection team discovered many very strange situations.
For example...
The body of native donkeys produces a small amount of calcium thioglycolate, which is an ingredient in hair loss agents.
For another example, they discovered that a Light Point phenotype, referred to as the LP phenotype, will appear in native donkeys.
Under this phenotype.
Mutants of the MC1R gene not only affect hair, but also affect the amplification of the CDS sequence of the PepT1 gene.
This directly leads to a very strange ratio in the Young's elastic modulus of 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 decreased from 217:1 to 15:1.
Besides,
A pentose phosphate pathway product with 225 different metabolites from the high-tender group was also detected in the hair of local donkeys. The results of this study were also published in the Nature sub-journal.
Therefore, these phenotypes can be used as test points in the DNA sequencing process.
In a sense.
It is even easier to detect this phenotype in local and foreign donkeys than in normal humans and tumors.
"..."
After hearing what Xu Yun said.
The expression on Lao Guo's face also became hesitant.
seem.....
Does it really make sense?
After all, in order to ensure that they could have the "exclusive agency rights" for donkey pulp film, the Rabbits had indeed experimented with various varieties of foreign donkeys.
For example, Pakistani donkey, neon donkey, Egyptian donkey, etc.....
But after rounds of experiments, it turns out that only local donkeys can produce donkey pulp films that meet the requirements - otherwise the rabbits would not have the confidence to trade with it.
If we explain it from a genetic perspective, it seems that it can indeed be explained?
Then he pondered for a moment, decided to put the matter aside for now, and looked at Xu Yun again:
"Xiao Han, since the problem of DNA testing points can be solved with local donkeys, then you can finish the rest of the necessary things."
"If the conditions and equipment at the base meet the requirements, then we will start studying it immediately. If there is anything missing, we will contact the capital as soon as possible to supplement it."
Xu Yun immediately hummed after hearing this, thought for a moment, and explained:
"In addition to the structure and target, the remaining components of targeted drugs are enzymes and reagents in each link, which involves a lot of chemical steps..."
"After all, if the drug and target are to be combined, some specific enzymes are definitely needed for recognition and binding. In addition, if PCR technology is to complete amplification, it also requires DNA polymerase."
As soon as Xu Yun finished speaking.
Lao Guo nodded and expressed his understanding.
Although he had never been exposed to the concept of targeted drugs before, he still knew about enzymes.
The discovery of enzymes can be traced back to 1897, when German chemist Buchner extracted brewing enzyme from ground yeast cells that can ferment alcohol.
From then on.
The concept of enzymes entered the field 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 would win the Nobel Prize for this discovery.
Nowadays, enzyme production technology in the chemical industry has developed to a point where it is barely a self-contained system, even in China.
So when Lao Guo heard Xu Yun mention targeting enzymes, he quickly followed his lead.
Then Xu Yun paused and raised an index finger:
"First, let's talk about the enzymes required for PCR. This enzyme has actually been extracted in Europe, mainly from E. coli."
"As long as E. coli is cultured, centrifuged and extracted, this enzyme can be obtained."
As we all know.
The basic principle of PCR technology is the complementary pairing of primers and DNA template strands.
Then, the catalytic effect of enzyme is used in the PCR reaction system to amplify the template DNA to the specified multiple.
The first step in the PCR reaction is to separate the double-stranded DNA into two single strands, and then pair the primers with both ends of the DNA to form a starting structure of double-stranded DNA.
This chapter is not finished yet, please click on the next page to continue reading the exciting content! Next.
The auxiliary enzyme starts to synthesize the DNA strand downward from the starting structure of double-stranded DNA through DNA polymerization.
The most common enzyme in this regard in later generations is Taq enzyme, which is extracted from Thermus aquaticus and has a protein with strong resistance to high temperatures.
But on the other hand.
Its extraction technology requirements are very high, and a relatively complete extraction process will not appear until the late 1980s.
It's a coincidence.
In his previous life, when Xu Yun was writing a novel called "The Empire of Technology Begins from Local Donkeys", he happened to also write about hand-rubbed PCR technology.
As a result, I met a reader at that time. Xu Yun hadn't finished writing the plot, and he kept asking Taq enzyme how to solve it.
This is a typical speaking from God's perspective, because Xu Yuntmd has no intention of using Taq enzyme at all...
Compared with Taq enzyme, Klenow enzyme isolated from E. coli can achieve the same effect.
Actually.
When PCR technology was born, Klenow enzyme was used.
The extraction technology of this enzyme is very simple. All it takes is a centrifuge, and the rest of the steps can be easily handled.
However, compared to Taq enzyme, Klenow enzyme is not so resistant to high temperatures and is prone to denaturation.
That is to say, in the experiment, the enzyme must be added again in each cycle, which seriously hinders the popularization of PCR technology.
But the problem is that Xu Yun does not plan to promote PCR technology immediately. What he needs is to use this technology to produce targeted drugs for Yang Kaiqu to treat diseases.
Just like the Northern Song Dynasty copy Xu Yun's hand-made generator.
At that time, Xu Yun only had to ensure that he could provide electricity that could complete electrolysis, and he did not have to build a nuclear power plant.
In the Northern Song Dynasty, there was a wealthy local man named Lao Su who spread money, but now Xu Yun is backed by a huge country.
Although rabbits are still very poor these days, they still have the financial resources and ability to add Klenow enzyme to every cycle.
"Extract the enzyme from E. coli?"
Lao Guo blinked when he heard this and asked subconsciously:
"Xiao Han, centrifugation in the field of microbiology... This kind of operation 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 together in a short while?"
"sure."
Xu Yun nodded easily, without any wrinkles on his brows, and explained confidently:
"Gong Guo, although in terms of process, it requires a shaker and a high-precision filter membrane, it may be difficult to find equipment of the same standard in China."
"But on the other hand, although we don't have the same level of equipment, we do have more sophisticated instruments than this."
"A more sophisticated instrument?"
Lao Guo was slightly startled and could not follow Xu Yun's thoughts for a while.
But after all, he is a top-notch science and engineering expert, and centrifugation is also his area of proficiency, so he quickly realized something:
"You mean...the centrifuge from Jincheng 504 Factory and the batch of gas diffusion membranes?"
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 the 504 Factory.
After officially entering the core sequence of the base.
Xu Yun was finally told the [truth] about the gas diffusion membrane - although he had known about it for a long time...
This is a centrifuge used to enrich uranium. It is much better than any shaker...
In addition, only part of the gas diffusion membrane was used in the Zhuxianjian project, and now there are still thick piles piled in the warehouse of the 221 base.
Once these two problems are solved, the rest becomes much simpler.
For example, the eluent required by Klenow enzyme can be prepared with methanol, isopropyl alcohol, 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 an inherent smell.
So if nothing else happens, the ice cream business of Factory 504 may be affected in the future...
Then Xu Yun paused and continued:
"In addition to Pow enzymes, there are two sources of targeting enzymes required for targeted drugs."
"One is a synthetic metalloenzyme. I don't know the specific ingredients, but it is slightly more efficient than the second one."
"The other is a natural enzyme, which comes from marine actinomycetes - although the place where marine actinomycetes were found in the notebook was in the UK, you should be able to find this type of enzyme as long as you spend some time in the high latitudes of the country.
Bacteria.”
"Both enzymes can be used as recognition enzymes for targeted drugs. By adding these enzymes based on the drug structure as a reference to paclitaxel, the only remaining problem is clinical trials."
Students who were cancer cells in their previous lives should all know this.
In the development process of targeted drugs, metalloenzymes are a very common type of recognition enzymes.
They use active site metal ions for catalysis. More strictly speaking, metalloenzyme active site metal ions 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 2023 when Xu Yun traveled through.
About 70 small molecule inhibitors of metalloenzymes have been officially approved for clinical use.
Most of these inhibitors have direct coordination interactions with the active site metal ions through specific chemical types, often called metal-binding pharmacophore...which is what many people know as the life-or-death MBP.
Although Xu Yun did not give a specific formula out of the perspective of avoiding suspicion, there are only two types of metalloenzymes that can form a combination with the water-based structure of paclitaxel:
Boron or zinc.
Among them, boron Xu Yun estimates that domestic technology will not be able to successfully achieve a breakthrough, so the final choice should be zinc with a high probability.
This chapter is not over yet, please click on the next page to continue reading! As for the second natural enzyme...
Xu Yun said it was marine actinomycetes, but he actually meant marizomib, a cyclic peptide compound extracted from marine sponges.
It is the first compound that can inhibit the binding of ubiquitin-conjugating enzyme UBC13 to UEV1A, and can probably identify and inhibit the growth of 60 tumor cell lines.
There are actually quite a few places in China where marizomib can be extracted, mostly at high latitudes... Probably taking the city of Shanghai as the line, the corresponding targets can be found in the ocean above the city.
At the same time, in addition to marizomib, Flavopiridol, which can be extracted in Sange, is also a good choice.
However, rabbits must be developing in a low-key manner at this time, so Xu Yun finally gave up this idea.
Of course.
There are some aspects of the development of targeted drugs that Xu Yun can find solutions to, and there are others that he needs to bear the risks.
For example, diagnostic kits for targeted drugs, which are tools used to detect people who benefit from the drugs, involve nanotechnology and CTC. Xu Yun is really powerless in this regard.
At that time, he will at most use specific antibodies to conduct an enrichment test, and the accuracy will not exceed 80% at most.
In other words...
Even if the targeted drug is successfully produced, whether Yang Kaiqu can take it and the effect after taking it will all depend on his own physical constitution.
But what Xu Yun didn't know was.
Far away in the capital, the Pharmacy Institute of the Academy of Medical Sciences had already mastered a few small tablets a long time ago.
That's the fourth generation quinolone...
"...."
After Xu Yun finishes introducing this information.
Lao Guo subconsciously glanced at Lin Yu. Among the people present, this one was a well-deserved expert in medicine:
"Dr. Lin, what do you think?"
At this moment.
Lin Yu's expression was still a little shocked.
Although he had heard a lot about Xu Yun's strange things in the past few years, this was the first time he had experienced it personally.
He is indeed the legendary Mr. Deaf...
Fortunately, he was an old man who had seen a lot of storms, so he quickly came back to his senses.
He pondered for a moment, and finally a trace of determination flashed in his eyes and he 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 knowledge, he could not find anything to refute or question the specific principles.
In addition, Yang Kaiqu's current health has reached an extreme level, and he will definitely not be able to survive if he doesn't try. Maybe there will be a miracle if he tries.
To put it bluntly...
A dead horse is treated as a living horse doctor.
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:
"Friend Lai, to tell you the truth, if I had come to the base before, I would never have agreed to the country wasting these resources on me."
"But now that I have an obsession, I will shamelessly enjoy the preferential treatment for a while."
"Will there be any human clinical trials after this drug is ready? Then don't look for other people or donkeys, just conduct experiments and observations on me."
"If it works, I will try my best to survive. 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 a 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 contribution. I can only repay the country in this way."
The scene fell into silence, and Xu Yun was filled with emotions.
Yang Kaiqu in history also said this, and even more so. There are indeed quite a few people in this era who have a kind of sincerity and awareness that will move future generations.
About a minute passed.
Li Jue broke the silence in the ward when he spoke, and he spoke to Yang Kai with a solemn expression:
"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:
"If that's the case, then I'll wait and see!"
............
More than ten minutes later.
Yang Kaiqu's forced body entered a state of sleepiness again, and Li Jue and Lao Guo Xuyun took the initiative to say goodbye.
Then Li Jue took Lao Guo and Xu Yun to the factory office, and sent someone to invite Liu Youcheng from the chemical laboratory to start formulating the relevant report content.
Two hours later.
A telegram was transmitted to the capital.
Another hour passed.
A reply came from the capital:
[In principle, the targeted drug preparation plan is agreed, and relevant equipment and personnel will be delivered to the base in the near future].
Targeted drug development plan....
Now mount up!
.....................
Note:
There was no update yesterday because I rushed to a laboratory to observe the reappearance of room temperature superconductivity, which is the synthesis method of the rod. I won’t tell you which laboratory it is, but I will try to see if I can make a video or something.