Qianjiang Evening News·Hourly News Reporter Zhang Mijia
Everything can start with Professor Barry Sharples , who is 81 years old this year. His surname is Sharpless, and the word "insensitive, not smart".
But this old man, who is not smart, won the second Nobel Prize in Chemistry in his life today.
Beijing time on October 5, 2022, Royal Swedish Academy of Sciences announced that this year's Nobel Prize in Chemistry will be awarded to American scientists Carolyn R. Bertozzi, Denmark scientist Morten Meldal and American scientist K. Barry Sharpless, in recognition of their important research achievements in the field of click-through chemical biological orthogonal chemistry.
American scientist Carolyn R. Bertozzi, Danish scientist Morten Meldal and American scientist K. Barry Sharpless
click chemistry, and the bioorthogonal chemistry derived from it. Although most people don’t understand this, they can completely successfully judge that this year’s Nobel Prize Chemistry Award is another comprehensive science award!
There are currently various examples in many fields in the world, which have already shown the power of "click chemical reaction". However, Professor Sharples, who proposed "click chemistry", did not expect it to be used in the biological field at all.
"Kada"
In 2001, Barry Shaplers won the Nobel Prize in Chemistry for his outstanding achievements in the field of "chiral catalytic oxidation reaction".
When his life reached its peak, he was busy raising another seed:
At that time, Sharpple published an article in a scientific journal, advocating the adoption of a new minimalist method in chemistry. He believed that it was time for chemists to stop imitating natural molecules - this often makes it difficult for chemists to control the synthesis of molecules and also creates a huge obstacle in the development of new drugs.
In 2001, Sharplace proposed the concept of "click chemistry": a specific chemical reaction created by chemists can quickly and reliably splice molecular modules to complete various chemical synthesis.
We can understand this process as "building blocks": the snapping point "clicks" and the two reaction blocks synthesize new molecules.
click chemistry method is very accurate and efficient.
For example, if a person is born with two recessive pathogenic genes, there is a protein in the liver that makes glycogen , causing one of the synthetic branches to fail to function. In fact, this may be just a little change in the enzymes in the protein, but the result may lead to death.
Click chemistry by slightly changing the structure of these enzymes - this is not a difficult task for chemists, and maybe the patient only needs to come once a year - to keep the body normal.
This thing a chemist can do is a bit similar to repair work. But click chemistry is not about repairing genomic defects, and the engineering would be too big.
Some people say that Barry Sharples is like Mr. White in "Breaking Bad".
K.Barry Sharpless, born in 1941 in Philadelphia, Pennsylvania, USA, received his Ph.D. from Stanford University, California, USA in 1968. Professor WM Keck from the Cripps Research Center in La Jolla, California, USA.
Image source: WLA Forum
Copper Ion Help
Almost at the same time, in a laboratory in Denmark, Morton Meldar is developing ways to find potential drugs.
He built a huge molecular library that could contain hundreds of thousands of different substances, and then he began to screen them to see if any of them could block the pathogenic process.
In this process, he and his colleagues accidentally made triazole.
triazole is an ideal chemical structure unit. Its chemical structure is very stable and often appears in some drugs, dyes and agricultural chemicals.But chemists have tried to make triazoles using alkyne and azides, but this can lead to unnecessary by-products.
Motton Meldal and others found that copper ions can manipulate the progress of this reaction very effectively.
In June 2001, he first showed his discovery at a seminar on San Diego . In 2022, he published an article in an academic journal saying that the reaction could be used to bind many different molecules together.
It was the same year again, and Barry Shaplers (independent of Morton Meldal) also published a paper on the use of copper to catalyze the reaction of azides and alkynes. He described it as a “perfect click response.”
That is, if chemists want to connect two different molecules, they can relatively simply make one molecule have an azide group while introducing an alkynyl group into the other.
With the help of some copper ions, these two "building blocks" can be perfectly linked, "click".
Morten Meldal was born in Denmark in 1954 and received his Ph.D. from the Denmark Technical University in Lingbi, Denmark in 1986. Professor at the University of Copenhagen, Denmark. Image source: rtl
The simplicity of click reaction made it rapidly popular in laboratory research and industrial production.
has the "building block module" pioneered by Sharples and Meldal, and everyone can freely build their own "aircraft" and "cannons" -
click response helps produce new materials that need to meet specific needs. For example, manufacturers add azides that can react clicks in plastics or textiles, and later material upgrades can be simple—which may allow materials to conduct electricity, obtain sunlight, antibacterial, anti-UV radiation or substances with other ideal properties after being connected.
Heavy icing-coated
Professor Caroline Bertozzi came over from another direction to meet these two people.
Bertozzi is a chemical biologist. She has been studying "sugar" before -
Human cells are wearing glycoprotein coat, just like mm peanut chocolate beans.
glycoprotein is a cell's voice that contains information about many cells, such as it reveals a person's blood type .
glycoprotein may also tell us whether a person has cancer. When the cell turns from healthy to pathological, the "sugar coating" on its surface changes. One of these changes is the increase in the density of a specific glycoprotein called sialic acid .
This is a glycoprotein that can be found on every cell in your body. But for some reason, cancer cells, often contain more sialic acid than healthy cells.
Logically speaking, the human immune cell 's work is to taste all the cells in your body and eat those broken cells. Cancer cells should be eaten.
But immune cells will not be able to find that these cells are bad because cancer cells are rich in sialic acid, which makes them taste like healthy cells.
Bertozzi wants to use a method to track and strip off this coat of cancer cells.
Carolyn R. Bertozzi was born in the United States in 1966 and received his Ph.D. from the University of California, Berkeley in 1993. Professor Anne T. and Robert M. Bass, Stanford University, California, USA. Image source: wikipedia
Let immune cells have a good meal
Bertozzi uses click chemistry.
She connects fluorescent molecules to a biological "grab handle". When two blocks are combined, the fluorescence can mark the position of the glycan caught by the grasper in the cell.
But the "perfect" click chemistry will have a little flaw here: copper is toxic to organisms.
When she performed a copper-free click reaction test in a cell experiment, the azide and alkynyl groups could still react in an almost explosive manner.
In 2004, she published this result, creating the Nobel Prize-winning working term—the reaction between the gripper and the fluorescent molecule must be "bio-orthogonal".
In this long and focused development work, Bertozi always honestly follows the boring scientific research process, find documents, and do experiments.
Bertozzi's laboratory has developed a new type of biological drugs, which are equivalent to lawn mowers on the surface of cells - allowing drug particles to enter the surface of cancer cells and remove these sialic acids, so that the immune system can swallow cancer cells accurately and efficiently regardless of these glycoproteins, and enjoy these delicious snacks.
Image source: dnyuz
Grandpa Sharplas, who is "not smart", said he did not expect that click chemistry would be used in the biological field.
But in fact, the old man was originally a pre-med student. "But then my professor said, "You might as well try to study chemistry for a year, you will likely fall in love with chemistry." The instructor contacted him with a professor at Stanford. Sharplace, a graduate student who did not apply for chemistry, was admitted.
"I originally thought I was going to be a fisherman in New Jersey - because I failed a physical chemistry exam, I couldn't go into the lab to work."
And Sharples was being chased by a girl at that time - but in the end she really became Mrs. Sharples.
"So, I almost didn't take the chemistry path, but I finally chose to do chemistry research, which is a very correct thing."
But the old man still thinks "sharpless" is his best label. "Most of the time I think I'm stupid because I talk too much. My wife doesn't like to listen to me, but she has endured it for many years."
But today, we all want to pay deep tribute to these "unclear" scientists: they invented extremely simple and convenient tools to benefit all mankind.
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