How can polypeptide drugs help the treatment of many diseases?

Peptides have become ideal drug molecules because of their advantages of high affinity, high selectivity, low toxicity and easy synthesis Scientists have also developed new peptide drugs which can treat many diseases based on peptide molecules In this paper, the research progress of peptide drugs in treating diseases in recent years has been sorted out and shared with you! 　　   [1] cancer cell: Chinese scientists develop polypeptide drugs that can accurately treat prostate cancer 　　DOI：10.1016/j.ccell.2017.02.017 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 can target gene mutations that occur in about half of prostate cancer When TMPRSS2 and ERG genes are relocated and fused on the chromosome, prostate cancer development will be initiated However, the development of small molecular inhibitors targeting ERG has been a great challenge In this study, the researchers used macromolecular polypeptides to target ERG, and they proved in cell lines and animal models that this method can effectively target and promote the degradation of ERG fusion protein, with little impact on the normal function of cells "Targeting the expression products of this fusion gene is a big challenge We have solved this problem from another perspective " Said arul M chinaiyan, the author of the article [2] Wuhan virus successfully blocked JE and Zika virus infection by peptide inhibitors 　　doi：10.1016/j.antiviral.2017.02.009 Japanese encephalitis virus (JEV) and Zika virus (zikv) belong to Flaviviridae of Flaviviridae, which are arboviruses transmitted by mosquitoes JEV induced encephalitis B has a high rate of death and disability China is a high incidence area of JE, and the number of patients once accounted for 80% of the world's total The use of JEV vaccine has reduced the incidence rate of encephalitis B to some extent However, for the patients who have already been infected, there is still no specific drug or treatment for JEV Since May 2015, zikv began to break out in Brazil and spread rapidly to tropical and temperate regions In addition to mosquito borne transmission, zikv can also be transmitted from person to person through sexual transmission or mother to child vertical transmission, resulting in neonatal microcephaly In February 2016, the World Health Organization (who) declared the zikv epidemic as an "international health emergency" Although the who announced the lifting of the alert in November of the same year, it stressed that the international community still needs to be prepared for a "long-term war" with zikv Therefore, it is an urgent task to find effective drugs for JEV and zikv infection The envelope protein E of flavivirus plays an important role in the process of virus entry into cells E protein is divided into three domains domain I, II and III there is a stem region composed of two α helices between domain III and transmembrane domain In the process of the fusion of virus envelope and cell membrane, the stem area breaks back and fills the gap of E protein domain II in a way similar to "zipper" It draws the virus envelope close to the cell membrane and drives the fusion of the membrane 　　   [3] nature subjournal: a magic peptide that can effectively deal with drug-resistant bacteria 　　doi：10.1038/srep35465 The abuse of antibiotics around the world has received a lot of attention recently Because of overuse of antibiotics, more and more bacteria are resistant to antibiotics, resulting in the emergence of "super bacteria" At the same time, the development of new antibiotics has not kept pace with the evolution of bacteria According to the World Health Organization, by 2050, 10 million people may die of drug-resistant bacteria every year In order to update the arsenal for dealing with bacteria, some scientists have taken different measures Instead of developing and improving traditional antibiotics, they turned their attention to natural antimicrobial substances, some of which are protein fragments, called peptides Recently, researchers from the Massachusetts Institute of technology, Brasilia University and British Columbia University of Canada jointly designed an antibacterial peptide, which can eliminate many kinds of bacteria, including drug-resistant bacteria This achievement was published in scientific reports, a journal of Nature Publishing Group [4] NAT commun: scientists develop "super" peptide to deliver drugs to brain injury sites 　　doi：10.1038/ncomms11980 Scientists from the Sanford Burnham prebys medical discovery Institute in the United States recently published a new research progress, they developed a new technology for the treatment of traumatic brain injury The results were published in the international academic journal Nature communication, which provides a new way to deliver drugs to the brain injury site In the United States, about 2.5 million people suffer traumatic brain damage every year due to car accidents, falls or violent factors At present, the main intervention method for acute brain injury is to reduce intracranial pressure to maintain blood flow, but up to now, there are no approved drugs that can prevent the occurrence of cascade events that cause secondary injury There are more than 100 kinds of small molecular compounds in preclinical trials to alleviate the secondary brain injury after the initial injury These candidate drugs can block the occurrence of secondary injury events caused by inflammation, high levels of free radicals, neuron overexcitation and apoptosis signals 　　   [5] J Immunol: synthetic peptide targeting CD36 inhibits inflammatory response 　　doi：10.4049/jimmunol.1401028 Apolipoproteins are proteins that interact with lipoproteins They can stabilize the structure of lipoproteins and mediate receptor dependent recognition of lipoproteins (such as LDLR and B-type scavenger receptor) ApoA-I is the main component of HDL, which plays an important role in cholesterol reverse transport and anti-inflammatory The level of HDL in mice overexpressed with apoA-I increased significantly, while the chronic inflammation and cardiovascular sclerosis decreased significantly This effect depends in part on the ability of apoA-I to block the signal transduction process of damp Previous studies have found that a group of amphiphilic peptides called "SAHP" (an analog of apoA-I) can competitively bind to a variety of apoA-I receptors, including SR-BI, SR-BII and CD36 Sr-b may play an important role in the pathogenesis of acute lung disease because it is widely expressed on the surface of pulmonary epidermal cells and macrophages Furthermore, apoA-I and SAHP may have some influence on the function of epidermal cells [6] blood: peptide drugs are expected to treat rare anemia and polycythemia at the same time 　　doi：10.1182/blood-2015-10-676742 A new study has found that a synthetic peptide called minihepcidins may have potential therapeutic effects on two serious blood diseases, namely β - thalassemia and polycythemia vera Although these two diseases have opposite effects on erythropoiesis, minihepcidins can help to restore the normal level of erythrocytes and relieve the abnormal enlargement of spleen At the same time, in β - thalassemia, the drug can also control the excessive accumulation of iron ions and avoid the serious toxic effects caused by excessive iron ions "It seems counterintuitive that a compound can treat two distinct diseases at the same time, but by limiting the absorption of iron ions, this compound can normalize the level of red blood cells in animal models If these preclinical results can be transformed into human beings, it will provide new treatment options for the treatment of these two blood diseases "Stefano rivella, the author of the paper, said that recently the relevant research results were published in the international academic journal blood 　　   [7] Cancer Res: peptide drug release protein interaction inhibits cancer cell metastasis 　　doi：10.1158/0008-5472.CAN-15-1680 Recently, researchers from the University of Augusta in the United States found that a gene called WASF3 is continuously expressed in cancer cells, but in a silent state in healthy cells, which may become an important target to reduce the metastasis ability of cancer cells Previous studies have found that WASF3 protein can promote the invasion of cancer cells Recently, scientists have found that it can inhibit the transfer ability of highly invasive human breast and prostate cancer cells by blocking the interaction between the protein and another protein to help maintain its function In the latest study, published in the international academic journal Cancer Research, the researchers demonstrated that blocking the interaction between WASF3 and Cyfip1 can inhibit the function of WASF3 Cyfip1 can help stabilize the protein complex, and only when the two are combined can they remain stable The team found the gene in a child with neuroblastoma in 2002, when they suspected that WASF3 might play an important role in cancer metastasis Later, they knocked out the gene in the cell and found that it could prevent the spread of cancer cells Later, they found that WASF3 could interact with Cyfip1 through mass spectrometry, and it was stable [8] new peptide can treat heart attack and stroke Stroke, heart attack and traumatic brain injury seem to have little relevance, but they often have some common pathological manifestations, and the final results are the same, that is, cell death, and patients often lead to hypoxia and lead to body damage; In these diseases, the tissues affected by the lack of blood supply will open molecular signal pathways to stop the generation of energy Recently, researchers from the University of bangulion are looking for the human in derivative (human in is a neuroprotective factor), and find that a natural peptide encoded by the mitochondrial genome in the cell can successfully block the above process Professor Abraham parola, the researcher, said that the current research provides new hope for the development of new drug therapy to treat necrosis related diseases, such as traumatic brain injury, stroke and myocardial infarction, and there is no effective therapy to treat these diseases Humanin derivatives can play a role by neutralizing the decrease of ATP level caused by necrosis In this paper, the researchers tested the efficiency of human analog AGA (C8R) - hng17 and aga-hng by using the newly discovered natural polypeptides to treat the neurons exposed to necrosis factor The experimental results showed that it was effective 　　   [9] the US FDA awarded almac the orphan drug status of the first therapeutic polypeptide alm201 in the treatment of ovarian cancer Original source: almac discovery is granted orphan drug design for alm201 program in ovarian cancer Almac discovery, a British biopharmaceutical company based in Northern Ireland, focuses on the discovery and identification of innovative therapies for cancer treatment Recently, the company announced that the U.S Food and Drug Administration (FDA) has granted its experimental drug alm201 the status of orphan drug in the treatment of ovarian cancer Alm201 is a first-in-class therapeutic peptide, which is developed to simulate some properties of fkbpl Alm201 was originally developed based on