Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Simpler Way of Making Proteins Could Lead to New Nanomedicine Agents

23.02.2011
Researchers have developed a simple method of making short protein chains with spiral structures that can also dissolve in water, two desirable traits not often found together. Such structures could have applications as building blocks for self-assembling nanostructures and as agents for drug and gene delivery.

Led by Jianjun Cheng, a professor of materials science and engineering at the University of Illinois, the research team will publish its findings in the Jan. 22 edition of the journal Nature Communications.

Materials scientists have been interested in designing large polymer molecules that could be used as building blocks for self-assembling structures. The challenge has been that the molecules generally adopt a globular, spherical shape, limiting their ability to form orderly aggregates. However, polypeptides – chains of amino acids such as proteins – can form helical structures. Short polypeptide chains that adopt a spiral shape act like cylindrical rods.

“If you have two rigid rods, one positive and one negative, right next to each other, they’re going to stick to each other. If you have a way to put the charge on the surface then they can pack together in a close, compact way, so they form a three-dimensional structure,” Cheng said.

However, it is difficult to make helical polypeptides that are water-soluble so they can be used in solution. Polypeptides gain their solubility from side chains – molecular structures that stem from each amino acid link in the polypeptide chain. Amino acids with positive or negative charges in their side chains are needed to make a polypeptide disperse in water.

The problem arises when chains with charged side chains form helical structures. The charges cause a strong repulsion between the side chains, which destabilizes the helical conformation. This causes water-soluble polypeptides to form random coil structures instead of the desired helices.

In exploring solutions to the riddle of helical, water-soluble polypeptides, researchers have tried several complicated methods. For example, scientists have attempted grafting highly water-soluble chemicals to the side chains to increase the polypeptides’ overall solubility, or creating helices with charges only on one side.

“You can achieve the helical structure and the solubility but you have to design the helical structure in a very special way. The peptide design needs a very specific sequence. Then you’re very limited in the type of polypeptide you can build, and it’s not easy to design or handle these polypeptides,” Cheng said.

In contrast, Cheng’s group developed a very straightforward solution. Since the close proximity of the charges causes the repulsion that disrupts the helix, the researchers simply elongated the side chains, moving the charges farther from the backbone and giving them more freedom to keep their distance from one another.

The researchers observed that as they increased the length of the side chains with charges on the end, the polypeptides’ propensity for forming helices also increased.

“It’s such a simple idea – move the charge away from the backbone,” Cheng said. “It’s not difficult at all to make the longer side chains, and it has amazing properties for winding up helical structures simply by pushing the distance between the charge and the backbone.”

The group found that not only do polypeptides with long side chains form helices, they display remarkable stability even when compared to non-charged helices. The helices seem immune to temperature, pH, and other denaturing agents that would unwind most polypeptides.

This may explain why amino acids with large hydrophobic side chains are not found in nature. Such immutability would preclude dynamic winding and unwinding of protein structures, which is essential to many biological processes. However, rigid stability is a desirable trait for the types of applications Cheng’s group explores: nanostructures for drug and gene delivery, particularly targeting cancerous tumors and stem cells.

“We want to test the correlation of the lengths of the helices and the circulation in the body to see what’s the impact of the shape and the charge and the side chains for clearance in the body,” Cheng said. “Recent studies show that the aspect ratio of the nanostructures – spherical structures versus tubes – has a huge impact on their penetration of tumor tissues and circulation half-lives in the body.”

Cheng plans to create a library of short helical polypeptides of varying backbone lengths, side chain lengths and types of charge. He hopes to simplify the chemistry even further and make the materials widely accessible. His lab already has demonstrated that helical structures can be effective gene delivery and membrane transduction agents, and building the library of soluble helical molecules will allow further investigation of tailoring such nanostructures for specific biomedical applications.

The National Science Foundation and the National Institutes of Health supported this work. Illinois co-authors were graduate students Hua Lu and Yugang Bai and undergraduate student Jason Lang. “Hua Lu, a fifth year graduate student in my group, is the first author of the publication and made the most significant contribution to this work,” Cheng said. Yao Lin and Jin Wang, of the University of Connecticut, and professor Shiyong Liu, of the University of Science and Technology of China, also collaborated with Cheng’s group on the paper.

Liz Ahlberg | University of Illinois
Further information:
http://www.illinois.edu

More articles from Materials Sciences:

nachricht Move over, Superman! NIST method sees through concrete to detect early-stage corrosion
27.04.2017 | National Institute of Standards and Technology (NIST)

nachricht Control of molecular motion by metal-plated 3-D printed plastic pieces
27.04.2017 | Ecole Polytechnique Fédérale de Lausanne

All articles from Materials Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Fighting drug resistant tuberculosis – InfectoGnostics meets MYCO-NET² partners in Peru

28.04.2017 | Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

 
Latest News

Wireless power can drive tiny electronic devices in the GI tract

28.04.2017 | Medical Engineering

Ice cave in Transylvania yields window into region's past

28.04.2017 | Earth Sciences

Nose2Brain – Better Therapy for Multiple Sclerosis

28.04.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>