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SAN FRANCISCO， March 22 (Xinhua) -- Researchers have found a small molecule that was able to block the production of a specific protein involved in low-density lipoprotein (LDL) turnover by stalling only the ribosome that produces that protein.
Reported in the journal PLOS Biology， the discovery of the chemical compound， which halted the production of a small set of proteins while leaving general protein production untouched， suggests a new drug search strategy: find compounds that target undesired proteins before they are even made.
Many of today's therapies for cancer or heart disease are monoclonal antibodies that bind and disable proteins outside the cell. The immunotherapeutic checkpoint inhibitors block suppressor proteins， unleashing the immune system to attack cancer. But they aren't effective against all proteins， can't enter cells and must be delivered via injection.
Ribosomes are large， general-purpose molecular machines that translate genetic instructions in the form of messenger RNA into the proteins used to build cells， the enzymes in charge of cellular housekeeping， and the hormones that carry messages in and between cells. While antibiotics are known to stall the ribosome， they halt production of most proteins， explained Jamie Cate， a University of California， Berkeley， professor of molecular and cell biology and of chemistry.
In the study by Cate and his colleagues at UC Berkeley and Pfizer Worldwide Research and Development， the small molecule， when delivered orally to rats， lowered LDL cholesterol levels， much the way statins do， though by a different mechanism: by lowering the production of the protein PCSK9， short for proprotein convertase subtilisin kexin 9. The chemical stalls the ribosome only when it's producing PCSK9 and a couple of dozen other proteins out of the tens of thousands of proteins the body produces， as shown by a relatively new technique called ribosomal profiling.
Knocking out PCSK9 is known to lower blood levels of LDL cholesterol， the so-called bad cholesterol， presumably lowering risk of cardiovascular disease.
"PCSK9 was just where we started. Now we can think about how to come up with other small molecules that hit proteins that nobody has been able to target before because， maybe， they have a floppy part， or they don' t have a nook or cranny where you can bind a small molecule to inhibit them，" Cate was quoted as saying in a news release from UC Berkeley. "This research is saying， we may be able to just prevent the synthesis of the protein in the first place."
Suspecting that the small molecule， a multi-ringed chlorinated compound， could serve as a template， like a key blank that can be machined to open a specific lock， Cate said "we now have this key blank that we can cut in a number of different ways to try to go after undruggable proteins in a number of different disease states."
The molecule was discovered by Pfizer labs through live-cell screening for compounds that lower production of the protein PCSK9， which regulates the recycling of the LDL receptor.
CHONGQING Khris Middleton Womens Jersey , March 29 (Xinhua) -- Southwest China's Chongqing city will build a museum featuring history and objects related to weapon production during the country's war against Japanese troops from 1931 to 1945.
The facility, with a planned exhibition area of 12,000 square meters Giannis Antetokounmpo Womens Jersey , will be constructed based on the ruins of a wartime ordnance manufacturing site encompassing 25 production units in today's Jiulongpo District.
Over 40,000 exhibits, to be held in eight halls Jabari Parker Womens Jersey , will debut when the museum opens during National Day holiday in October.
Chongqing used to be a major production base for all kinds of weapons, including cannons, grenades and guns Eric Bledsoe Womens Jersey , during the 14-year Chinese People's War of Resistance Against Japanese Aggression starting in 1931.
TEHRAN, Sept. 25 (Xinhua) -- Iran's Foreign Ministry on Monday said that the Islamic republic insists on the national sovereignty and territorial integrity of Iraq.
Iran does not accept any move which undermines the stability, security and integrity of Iraq Authentic Khris Middleton Jersey , Foreign Ministry Spokesman, Bahram Qasemi, said at his weekly press conference.
Qasemi made the remarks with reference to the independence referendum underway in Iraq's northern Kurdistan region.
The decision by the Kurdish authorities to hold the vote might have unprecedented consequences for both the regional people and the Kurds themselves Authentic Giannis Antetokounmpo Jersey , he added.
Iran has constantly been in contact with the Kurdish officials, and has insisted that the Kurdish region should have solved its problems with Baghdad central government through political dialog, the spokesman said.
Iran believes that the unilateral move by Iraq's Kurdistan is taking place in an improper time without the necessary prudence Authentic Jabari Parker Jersey , he said, stressing that the move undermines the central government's achievements in the fight against terrorism.
Iranian President Hassan Rouhani and his Turkish counterpart Recep Tayyip Erdogan on Monday discussed the Iraqi Kurdistan independence referendum on the phone, and both sides emphasized their coordinated opposing stance over the referendum.
The integrity of Iraq is highly important for Iran Authentic Eric Bledsoe Jersey , Rouhani said, adding that the security of his country and the region is, to a significant degree Khris Middleton Jersey , depends on this factor.
This is a clear message for those who are going to disturb the security and stability of the region, Rouhani pointed out.
In another telephone conversation with Iraqi Prime Minister Haider al-Abadi on Sunday, Rouhani said that Iran was against any move that would undermine Iraq's territorial integrity and national unity.
Workers set up large flower terrace on Tian'anmen Square in Beijing
Scenery of terraced fields in Houyuan Village Giannis Antetokounmpo Jersey , China's Fujian
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