Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Uncharted Territory: Scientists Sequence the First Carbohydrate Biopolymer

11.10.2011
DNA and protein sequencing have forever transformed science, medicine, and society. Understanding the structure of these complex biomolecules has revolutionized drug development, medical diagnostics, forensic science, and our understanding of evolution and development. But, one major molecule in the biological triumvirate has remained largely uncharted: carbohydrate biopolymers.

Today, for the first time ever, a team of researchers led by Robert Linhardt of Rensselaer Polytechnic Institute has announced in the October 9 Advanced Online Publication edition of the journal Nature Chemical Biology the sequence of a complete complex carbohydrate biopolymer. The surprising discovery provides the scientific and medical communities with an important and fundamental new view of these vital biomolecules, which play a role in everything from cell structure and development to disease pathology and blood clotting.


Rensselaer Polytechnic Institute
Structure of the bikunin. The portion on the left corresponds to the sugar part of the molecule, the sequence of which was determined in the current study. The portion on the right corresponds to the protein part of bikunin.
Nature Chemical Biology

The paper is titled “The proteoglycan bikunin has a defined sequence.”

“Carbohydrate biopolymers, known as glycosaminoglycans, appear to be really important in how cells interact in higher organisms and could explain evolutionary differences and how development is driven. We also know that carbohydrate chains respond to disease, injury, and changes in the environment,” said Linhardt, who is the Ann and John H. Broadbent Jr. ’59 Senior Constellation Professor of Biocatalysis and Metabolic Engineering at Rensselaer. “In order to understand how and why this all happens, we first need to know their structure. And today, at least for the simplest glycosaminoglycan structure, we can now do this.”

The first glycosaminoglycan sequenced was obtained from bikunin. Bikunin is a proteoglycan, a protein to which a single glycosaminoglycan chain is attached. Unlike less sophisticated carbohydrate biopolymers, such as starch and cellulose, the proteoglycans are decorated with structurally complex carbohydrates that enable them to perform more sophisticated and defined roles in the body. Bikunin, for example, is a natural anti-inflammatory that is used as a drug for the treatment of acute pancreatitis in Japan. It has the simplest chemical structure of any proteoglycan. Linhardt views the discovery of the structure of bikuin as the first step on the ladder to the discovery of the structure of more complex proteoglycans.

“The first genome sequences of DNA were on the simplest organisms such as bacteria. Once the technology was developed it ultimately led to the sequencing of the human genome,” he said. “In our efforts to sequence carbohydrate biopolymers we don’t yet know if the defined structure we observe for this simple protoglycan will hold for much more complex proteoglycans.”

But, looking for structure in more complex proteoglycans will be among the next steps in the research for Linhardt and his team. The search for structure could help put to rest a long-running debate in the scientific community as to whether complex carbohydrate biopolymers require a defined structure to function.

“Despite all that is known about glycan formation, our understanding has not yet been deep enough to infer sequence or even determine if sequence occurs,” Linhardt said. “These findings represent a new way of looking at these complex biomolecules as ordered structures.”

Linhardt’s research into carbohydrate sequencing began 30 years ago. In his previous work, he determined that some order existed in at least a portion of some carbohydrate biopolymers, but it did not represent the entire finished puzzle.

“Previously, we could see a pattern, but we could not see if all the chains were playing the same music. The tools did not yet exist. Now we can recognize it as a symphony.”

To uncover the entire structure, Linhardt and his team, which was led by his doctoral student Mellisa Ly, borrowed a technique from the field of protein research called the proteomics top-down approach. As opposed to the bottom-up approach that first breaks apart a complex biopolymer into pieces and then rebuilds it piece by piece like a jigsaw puzzle, the top-down approach used by Linhardt and colleagues allows the researcher to picture the whole intact puzzle. This can only be accomplished with some of the most sophisticated technology available to the scientific community today, including very high-powered mass spectrometers.

Linhardt used a mass spectrometer located in the Rensselaer Center for Biotechnology and Interdisciplinary Studies (CBIS) to make his initial discoveries, and had these results independently confirmed on a separate and higher-level spectrometer at the University of Georgia. Mass spectrometers break down a molecule into separate charged particles or ions. These ions can then be categorized and analyzed based on their mass-to-charge ratio. These ratios then allow for sequencing of the entire molecule.

“This was truly the convergence of really sophisticated spectroscopy and its application to biology,” Linhardt said. “We were fortunate to have a lot of time to play with the instrument at CBIS to understand its capabilities.”

Beyond the technology it also took faith and determination. According to Linhardt, “It takes a student that is willing to try something even when the odds are pretty low. If it doesn’t work, you make incremental progress. If it does work, you can make a great discovery. But, from the beginning you need to be a believer that it is worth taking the chance because it takes a lot of hard work in the lab.”

And the odds weren’t in Linhardt’s favor. Despite being the most simple of proteoglycans, there were still 290 billion different possible sequences for the molecule.

“The first sample we looked at, we got the structure,” Linhardt said. “In the end we did 15 chains and they all came back playing the same exact symphony.”

The research is funded by the National Institutes of Health.

Linhardt and Ly were joined in the research by Tatiana Laremore of Rensselaer; Franklin Leach and Jonathan Amster of the University of Georgia; and Toshihiko Toida of Chiba University in Japan.

Gabrielle DeMarco | Newswise Science News
Further information:
http://www.rpi.edu

Further reports about: Bikunin Biopolymer CBIS Carbohydrate DNA genome sequence mass spectrometer territory

More articles from Life Sciences:

nachricht Solving the efficiency of Gram-negative bacteria
22.03.2019 | Harvard University

nachricht Bacteria bide their time when antibiotics attack
22.03.2019 | Rice University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: The taming of the light screw

DESY and MPSD scientists create high-order harmonics from solids with controlled polarization states, taking advantage of both crystal symmetry and attosecond electronic dynamics. The newly demonstrated technique might find intriguing applications in petahertz electronics and for spectroscopic studies of novel quantum materials.

The nonlinear process of high-order harmonic generation (HHG) in gases is one of the cornerstones of attosecond science (an attosecond is a billionth of a...

Im Focus: Magnetic micro-boats

Nano- and microtechnology are promising candidates not only for medical applications such as drug delivery but also for the creation of little robots or flexible integrated sensors. Scientists from the Max Planck Institute for Polymer Research (MPI-P) have created magnetic microparticles, with a newly developed method, that could pave the way for building micro-motors or guiding drugs in the human body to a target, like a tumor. The preparation of such structures as well as their remote-control can be regulated using magnetic fields and therefore can find application in an array of domains.

The magnetic properties of a material control how this material responds to the presence of a magnetic field. Iron oxide is the main component of rust but also...

Im Focus: Self-healing coating made of corn starch makes small scratches disappear through heat

Due to the special arrangement of its molecules, a new coating made of corn starch is able to repair small scratches by itself through heat: The cross-linking via ring-shaped molecules makes the material mobile, so that it compensates for the scratches and these disappear again.

Superficial micro-scratches on the car body or on other high-gloss surfaces are harmless, but annoying. Especially in the luxury segment such surfaces are...

Im Focus: Stellar cartography

The Potsdam Echelle Polarimetric and Spectroscopic Instrument (PEPSI) at the Large Binocular Telescope (LBT) in Arizona released its first image of the surface magnetic field of another star. In a paper in the European journal Astronomy & Astrophysics, the PEPSI team presents a Zeeman- Doppler-Image of the surface of the magnetically active star II Pegasi.

A special technique allows astronomers to resolve the surfaces of faraway stars. Those are otherwise only seen as point sources, even in the largest telescopes...

Im Focus: Heading towards a tsunami of light

Researchers at Chalmers University of Technology and the University of Gothenburg, Sweden, have proposed a way to create a completely new source of radiation. Ultra-intense light pulses consist of the motion of a single wave and can be described as a tsunami of light. The strong wave can be used to study interactions between matter and light in a unique way. Their research is now published in the scientific journal Physical Review Letters.

"This source of radiation lets us look at reality through a new angle - it is like twisting a mirror and discovering something completely different," says...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

International Modelica Conference with 330 visitors from 21 countries at OTH Regensburg

11.03.2019 | Event News

Selection Completed: 580 Young Scientists from 88 Countries at the Lindau Nobel Laureate Meeting

01.03.2019 | Event News

LightMAT 2019 – 3rd International Conference on Light Materials – Science and Technology

28.02.2019 | Event News

 
Latest News

Solving the efficiency of Gram-negative bacteria

22.03.2019 | Life Sciences

Bacteria bide their time when antibiotics attack

22.03.2019 | Life Sciences

Open source software helps researchers extract key insights from huge sensor datasets

22.03.2019 | Information Technology

VideoLinks
Science & Research
Overview of more VideoLinks >>>