Polypeptide drugs Important research achievements focus on new progress in the field of peptide drug molecular research!

In this paper, a number of important research results have been compiled to focus on the new progress made by scientists in the field of peptide drug molecular research!

【1】 Science sub: m3mp6 peptide loaded nanoparticles are expected to treat heart disease

In a new study, researchers from the University of Illinois at Chicago have developed a new drug that prevents blood clots without increasing the risk of bleeding, a common side effect of all antiplatelet drugs. The results were published in the journal Science Translational Medicine.

The new study describes the drug and its delivery mechanism, and points out that it is also an effective treatment for heart disease in animal models. “Unfortunately, current antiplatelet drugs can prevent the formation of blood clots that cause heart disease and stroke, but they can also damage the ability of platelets to stop bleeding if blood vessels break,” Du said. In some cases, severe bleeding can be life-threatening. What’s amazing about this new drug is that it prevents blood clots, but it doesn’t make people bleed easily, which other drugs can’t do

【2】 Chem commun: a novel peptide molecule for the treatment of gastrointestinal disorders

TFF1 peptide is a key participant in mucosal protection and repair. In a recent study, a team led by Markus muttenthaler of the Department of chemistry at the University of Vienna successfully synthesized and folded TFF1 peptides for the first time. Three known trefoil family peptides TFF1, TFF2 and TFF3 are mainly produced by gastrointestinal mucosa. It is named after its trilobal folded structure.

Studies have shown that these peptides are products of local resistance to inflammation and gastrointestinal injury by accelerating wound healing, and they have great potential for the treatment of gastrointestinal and other mucosal diseases, such as dry eye disease and asthma.

“To date, there are two oral peptide therapeutics on the market for diseases such as irritable bowel syndrome,” says muttenthaler. Because of their relatively large size, they are not absorbed into the blood through the wall of the gastrointestinal tract, so they can only act locally in the gastrointestinal tract without serious side effects. “

【3】 Scientists have developed a new type of experimental peptide molecule, which may effectively target sars-cov-2 in the treatment of covid-19 infection

Recently, scientists from MIT and other institutions have designed a new type of peptide by studying the computer model of protein-protein interaction, which can bind coronavirus protein and decompose it through cellular pathway. This type of peptide may be used as a potential therapy to inhibit the replication of sars-cov-2 virus in infected cells.

The idea is to use a computer technology to engineer the peptide to treat covid-19, which can simply label and degrade the virus once it enters the cell.

Now that researchers have tested the new peptide in human cells, they are planning cell and animal studies to assess the efficacy of the peptide, and on June 1, researchers reported their preliminary findings in a preprint platform called biorxiv. Scientists are looking for a variety of strategies to develop new therapies for covid-19. One of the areas of interest is the development of specific antibodies to bind inactivated viral proteins, such as spinosin, which can be used by coronaviruses to enter human cells;

one way to correlate is to replace antibodies with small protein fragments called peptides MIT researchers are working on engineering the peptides to bind to the spinel proteins in cells and stimulate cells to break viral proteins. The idea is for peptides to recruit naturally occurring proteins called E3 ubiquitin ligase, which can be labeled and destroyed when cells no longer need them.

【4】 ACS Nano: researchers design peptide therapy for covid-19

Scientists around the world are searching for inhibitors of sars-cov-2. SARS-CoV-2 is a novel coronavirus that causes COVID-19 pandemic. Now, researchers report on ACS Nano that they have used computer modeling to evaluate four peptides that mimic the viral binding domain of human proteins, the key proteins that allow sars-cov-2 to enter cells.

In order to infect cells, sars-cov-2 uses its spike protein to bind to ACE2 receptor, a protein located on the surface of some human cells. This attachment allows the virus to fuse with the host cell membrane and enter. Many researchers have been trying to find compounds that block the key regions of the spike protein to prevent the virus from infecting cells. Yanxiao Han and Petr Kral wanted to use computer modeling to design compounds that mimic the natural target ACE2 of this spike protein.

【5】 Biorxiv: breakthrough! Synthetic peptide drugs can block the binding of sars-cov-2 virus to human cells

To develop a possible treatment for covid-19, a team of chemists at the Massachusetts Institute of technology designed a candidate drug that they believed would prevent coronavirus from entering human cells. The potential drug is a short protein fragment, or peptide, that mimics a protein found on the surface of human cells. Researchers have shown that their new peptide can bind to the viral protein used by coronavirus to enter human cells, thus potentially arming the protein.

“We have the main compound that we really want to explore, because it can actually interact with viral proteins in a way that we predict, so it has the opportunity to inhibit the virus from entering the host cell,” said Brad penteleute, associate professor of chemistry at the Massachusetts Institute of technology, who led the study.

The MIT team reported their preliminary findings in a preprint on biorxiv, an online preprint server, on March 20. They have sent samples of the peptide to partners who plan to test them in human cells.

【6】 PLoS pathway: novel engineering peptides may show potential long-term anti HIV potential

Recently, in a research report published in the international journal PLoS pathogens, scientists from Fudan University and other institutions found that a new engineering peptide-ibp-cp24 may be expected to be a long-term anti HIV drug, which can be used alone or with a wide range of neutralizing antibodies to treat and prevent HIV-1 infection.

In this study, the researchers pointed out that ibp-cp24 can exhibit a long half-life and potentially carry a wide range of anti HIV-1 activity, even against drug-resistant strains. Enviride is the first anti HIV peptide drug approved by FDA.

However, due to its short half-life and easy to produce drug-resistant HIV strains, its clinical application is often limited. In this study, researchers have developed a novel strategy that can extend the half-life of an anti HIV peptide called Cp24 by fusing it with a human immunoglobulin G (IgG) Fc binding peptide (IBP).

【7】 JCI: new discovery! A special peptide that can mimic beneficial cholesterol may be expected to reverse inflammatory bowel disease!

Recently, a report was published in the International Journal of clinical In the Research Report on investigation, scientists from the University of California found that a special peptide may mimic the function of high-density lipoprotein (HDL), which is a kind of beneficial cholesterol.

It may help to treat inflammation associated with inflammatory bowel disease (IBD). In the article, the researchers also revealed the molecular mechanism of inflammatory bowel disease and its therapeutic effect Other possible drugs.

Inflammatory bowel disease is a chronic inflammatory disease of digestive tract. The most common inflammatory bowel diseases include Crohn’s disease and ulcerative colitis. At present, there is almost no effective treatment for inflammatory bowel disease, and most patients eventually need surgical treatment.

Now researchers have found that compared with healthy people, the level of apoA-I protein in patients with inflammatory bowel disease is lower, and apoA-I is HDL In addition, apoA-I protein can also slow down the body’s inflammatory performance and act as an antioxidant in the body to inhibit cell damage.

【8】 ELife: Mini peptide can restore heart function in mice

According to a study by eLife, researchers have found a peptide molecule that can restore normal heart function in mice. This molecule works by preventing calcium regulation disorders and cardiac remodeling, and may be a promising new gene therapy target for heart failure.

In many processes leading to heart failure, the damage caused by calcium is the most prominent. The activity of calcium in and out of cells can make the heart muscle contract and relax. A calcium pump called SERCA controls the flow of calcium, but its effect is impaired in heart failure. Previous studies have suggested that enhancing SERCA activity can maintain cardiac contractility and treat heart failure.

Our laboratory recently discovered a peptide called dwarf open reading frame (dworf), which binds directly to SERCA and enhances its activity, “explains Catherine makarewich, a postdoctoral researcher at the University of Texas Southwest Medical Center. “In this study, we explored the therapeutic potential of high-level dworf as a way to increase SERCA activity and improve cardiac contractility in heart failure.

Previous work by the team has shown that dworf works by replacing molecules that inhibit SERCA, known as phosphoprotein (PIN). To further study this, they designed mice to have higher levels of dworf and / or pin in the heart, and then studied the effects.

【9】 Cancer cell: Chinese scientists develop peptide drugs for precise treatment of prostate cancer

In a new study recently published in the international academic journal Cancer Cell, researchers from the University of Michigan have developed a new treatment strategy that targets genetic mutations that occur in about half of prostate cancer.

When the two genes, TMPRSS2 and ERG, are repositioned on the chromosome and fused together, the development of prostate cancer is initiated. However, the development of small molecule inhibitors targeting ERG has always been a great challenge. In this study, researchers used macromolecular polypeptides to target ERG.

They have proved that this method can effectively target and promote the degradation of ERG fusion protein in cell lines and animal models, with little effect on the normal function of cells. “Targeting the expression product of this fusion gene is a big challenge. We have solved this problem from another angle. ” The author of the article, arul M. chinnaiyan, said.

Researchers have found that a group of peptides can specifically interact with ERG protein. They tested the peptides in cell lines that produced fusion gene products and found that they could disrupt ERG function. In cells that do not produce such fusion products, these peptides have little effect on gene expression. They also studied how these peptides affect the biological process of ERG regulation.

【10】 Metab engin: a novel peptide compound valinomycin is expected to treat sars-cov-2 infection

Researchers have been stepping up the production of a promising drug to effectively kill the SARS CoV virus in cell cultures. Now, the drug may also be effective against the infection of sars-cov-2, a close relative of SARS CoV. Recently, a report was published in the international magazine metabolic According to the research report in engineering, scientists from Northwestern University and Shanghai University of science and technology in China have developed a very potential molecule valinomycin in a cell-free system.

Based on this acellular system, researchers are expected to increase the production of valinomycin by more than 5000 times in a few short design cycles, At the same time, it also achieved a higher molecular concentration in cells than before.

Because we use this cell-free system, we can optimize the rate of production in cells to further increase valinomycin production. For example, the pathway optimization cycle takes days rather than weeks or months, which may be particularly important in response to epidemics such as the covid-19 epidemic.

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