Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Artificial Blood Maker: EPO

15.10.2012
First successful total synthesis of Erythropoietin

“Blood is quite a peculiar kind of juice“—that is what Mephisto knew, according to Goethe’s “Faust“. But if blood really is very special, then erythropoietin (EPO) must be a very special molecule, as it triggers the production of our red blood cells.



After ten years of intense research, American scientists have now succeeded in making a fully synthetic version of this special molecule. This achievement represents a landmark advance in the chemical synthesis of complex biological molecules from basic building blocks.

EPO is a hormone produced in the kidneys that induces the differentiation of bone marrow stem cells to erythrocytes (red blood cells). Upon sensing decreased oxygen in circulation, EPO is secreted to boost the production of red blood cells. EPO has found many therapeutic applications. Dialysis patients, whose haematosis is affected by renal failure, are treated with EPO and the drug is also given to cancer patients who have undergone chemotherapy or radiation therapy. Black sheep among racing cyclists, and other athletes, have abused EPO in an effort to improve their athletic performance.

Until now, only nature itself was able to synthesize EPO. For therapeutic use, the drug has to be produced biotechnologically in cell cultures. In a major breakthrough, a team led by Samuel J. Danishefsky at the Sloan-Kettering Institute for Cancer Research in New York has now produced a fully synthetic EPO by total synthesis in their lab. Because classical methods of protein synthesis were insufficient to build up this complex biomolecule, the scientists had to develop sophisticated new synthesis strategies to attain their objective.

EPO is not actually one compound but a large family of molecules. Known as glycoproteins, the structures are composed of a protein decorated with four carbohydrate sectors. The protein portion is always the same, as are the locations at which the carbohydrate domains are attached. Yet, in endogenous EPO protein, there are a wide variety of different carbohydrate sectors that may be appended to the protein. It has not been possible to access naturally occurring EPO as a homogeneous, pure molecule. By adopting the tools of chemical synthesis, the investigators were able to make, for the first time, pure “wild type” EPO glycoprotein incorporating the natural amino acid sequence and four carbohydrate sectors of strictly defined structure.

Extension of this strategy will enable scientists to make numerous versions of the molecule and to study how differences in the chemical structure of the carbohydrate domains may affect how the glycoprotein induces the production of red blood cells.

The structure of the synthetic EPO was verified by mass spectrometry. Tests using stem cells proved the effectiveness of the synthesized EPO: like its natural counterpart, the synthetic EPO triggered the formation of red blood cells from stem cells.

About the Author
Dr. Samuel Danishefsky is Centenary Professor of Chemistry at Columbia University and the Eugene Kettering Chair and Head of the Laboratory for Bioorganic Chemistry at the Sloan-Kettering Institute for Cancer Research in New York City. He is a member of the American Academy of Arts and Sciences and the National Academy of the Sciences and is a recipient of the Wolf Prize in Chemistry (with Prof. Gilbert Stork), the Franklin Medal in Chemistry, the Bristol Myers Squibb Lifetime Achievement Award in Chemistry, and the National Academy of Sciences Award in the Chemical Sciences. His research interests include the chemical synthesis of challenging small molecule and biologics-based compounds of therapeutic import.
Author: Samuel J. Danishefsky, Sloan-Kettering Institute for Cancer Research, New York (USA), http://www.mskcc.org/research/lab/samuel-danishefsky
Title: At Last: Erythropoietin as a Single Glycoform
Angewandte Chemie International Edition, Permalink to the article: http://dx.doi.org/10.1002/anie.201206090

Samuel J. Danishefsky | Angewandte Chemie
Further information:
http://pressroom.angewandte.org

More articles from Life Sciences:

nachricht Cells migrate collectively by intermittent bursts of activity
30.09.2016 | Aalto University

nachricht The structure of the BinAB toxin revealed: one small step for Man, a major problem for mosquitoes!
30.09.2016 | CNRS (Délégation Paris Michel-Ange)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: First-Ever 3D Printed Excavator Project Advances Large-Scale Additive Manufacturing R&D

Heavy construction machinery is the focus of Oak Ridge National Laboratory’s latest advance in additive manufacturing research. With industry partners and university students, ORNL researchers are designing and producing the world’s first 3D printed excavator, a prototype that will leverage large-scale AM technologies and explore the feasibility of printing with metal alloys.

Increasing the size and speed of metal-based 3D printing techniques, using low-cost alloys like steel and aluminum, could create new industrial applications...

Im Focus: New welding process joins dissimilar sheets better

Friction stir welding is a still-young and thus often unfamiliar pressure welding process for joining flat components and semi-finished components made of light metals.
Scientists at the University of Stuttgart have now developed two new process variants that will considerably expand the areas of application for friction stir welding.
Technologie-Lizenz-Büro (TLB) GmbH supports the University of Stuttgart in patenting and marketing its innovations.

Friction stir welding is a still-young and thus often unfamiliar pressure welding process for joining flat components and semi-finished components made of...

Im Focus: First quantum photonic circuit with electrically driven light source

Optical quantum computers can revolutionize computer technology. A team of researchers led by scientists from Münster University and KIT now succeeded in putting a quantum optical experimental set-up onto a chip. In doing so, they have met one of the requirements for making it possible to use photonic circuits for optical quantum computers.

Optical quantum computers are what people are pinning their hopes on for tomorrow’s computer technology – whether for tap-proof data encryption, ultrafast...

Im Focus: OLED microdisplays in data glasses for improved human-machine interaction

The Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP has been developing various applications for OLED microdisplays based on organic semiconductors. By integrating the capabilities of an image sensor directly into the microdisplay, eye movements can be recorded by the smart glasses and utilized for guidance and control functions, as one example. The new design will be debuted at Augmented World Expo Europe (AWE) in Berlin at Booth B25, October 18th – 19th.

“Augmented-reality” and “wearables” have become terms we encounter almost daily. Both can make daily life a little simpler and provide valuable assistance for...

Im Focus: Artificial Intelligence Helps in the Discovery of New Materials

With the help of artificial intelligence, chemists from the University of Basel in Switzerland have computed the characteristics of about two million crystals made up of four chemical elements. The researchers were able to identify 90 previously unknown thermodynamically stable crystals that can be regarded as new materials. They report on their findings in the scientific journal Physical Review Letters.

Elpasolite is a glassy, transparent, shiny and soft mineral with a cubic crystal structure. First discovered in El Paso County (Colorado, USA), it can also be...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Paper – Panacea Green Infrastructure?

30.09.2016 | Event News

HLF: From an experiment to an establishment

29.09.2016 | Event News

European Health Forum Gastein 2016 kicks off today

28.09.2016 | Event News

 
Latest News

First-Ever 3D Printed Excavator Project Advances Large-Scale Additive Manufacturing R&D

30.09.2016 | Materials Sciences

New Technique for Finding Weakness in Earth’s Crust

30.09.2016 | Earth Sciences

Cells migrate collectively by intermittent bursts of activity

30.09.2016 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>