Navigation Links
Simpler way of making proteins could lead to new nanomedicine agents
Date:2/23/2011

CHAMPAIGN, Ill. 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 Feb. 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.


'/>"/>

Contact: Liz Ahlberg
eahlberg@illinois.edu
217-244-0173
University of Illinois at Urbana-Champaign
Source:Eurekalert  

Related biology news :

1. Health diagnosis made simpler
2. Compound screening for drug development made simpler
3. New method for making tiny catalysts holds promise for air quality
4. Is our too clean culture making our kids sick?
5. Making school lunchrooms smarter
6. Making cookies that are good for your heart
7. A smart use for wisdom teeth: Making stem cells
8. Study: 3 out of 4 cats will wear a collar, making it worth a try
9. Plant scientists move closer to making any crop drought-tolerant
10. Toward making extended blood group typing more widely available
11. Making enough red blood cells
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Simpler way of making proteins could lead to new nanomedicine agents
(Date:6/2/2016)...   The Weather Company , an IBM Business (NYSE: ... capability in which consumers will be able to interact with ... via voice or text and receive relevant information about the ... Marketers have long sought an advertising solution that can create ... relevant and valuable; and can scale across millions of interactions ...
(Date:5/16/2016)... May 16, 2016   EyeLock LLC , a ... the opening of an IoT Center of Excellence in ... expand the development of embedded iris biometric applications. ... of convenience and security with unmatched biometric accuracy, making ... aside from DNA. EyeLock,s platform uses video technology to ...
(Date:4/28/2016)... First quarter 2016:   , ... the first quarter of 2015 The gross margin was ... 18.8) and the operating margin was 40% (-13) Earnings ... flow from operations was SEK 249.9 M (21.2) , ... SEK 7,000-8,500 M. The operating margin for 2016 is ...
Breaking Biology News(10 mins):
(Date:6/27/2016)... June 27, 2016  Global demand for enzymes ... through 2020 to $7.2 billion.  This market includes ... cleaning products, biofuel production, animal feed, and other ... and biocatalysts). Food and beverages will remain the ... increasing consumption of products containing enzymes in developing ...
(Date:6/27/2016)... ... June 27, 2016 , ... ... medical technologies, services and solutions to the healthcare market. The company's primary focus ... distribution, manufacturing, sales and marketing strategies that are necessary to help companies efficiently ...
(Date:6/24/2016)... DIEGO , June 24, 2016 ... more sensitively detects cancers susceptible to PARP inhibitors ... circulating tumor cells (CTCs). The new test has ... HRD-targeted therapeutics in multiple cancer types. ... targeting DNA damage response pathways, including PARP, ATM, ...
(Date:6/23/2016)... 23, 2016   Boston Biomedical , an ... designed to target cancer stemness pathways, announced that ... Orphan Drug Designation from the U.S. Food and ... cancer, including gastroesophageal junction (GEJ) cancer. Napabucasin is ... inhibit cancer stemness pathways by targeting STAT3, and ...
Breaking Biology Technology: