PRESS-NEWS.org - Press Release Distribution
PRESS RELEASES DISTRIBUTION

Better protein capture a boon for drug manufacturers

Rice University technique could widen bottleneck for pharmaceutical, other industries

2014-01-23
(Press-News.org) Contact information: David Ruth
david@rice.edu
713-348-6327
Rice University
Better protein capture a boon for drug manufacturers Rice University technique could widen bottleneck for pharmaceutical, other industries Rice University scientists have created a way to fine tune a process critical to the pharmaceutical industry that could save a lot of time and money.

A combination of the Rice technique that provides pinpoint locations for single proteins and a theory that describes those proteins' interactions with other molecules could widen a bottleneck in the manufacture of drugs by making the process of isolating proteins five times more efficient.

The work by Rice chemist Christy Landes and her team will be reported online this week in the Proceedings of the National Academy of Sciences.

A critical step in drug manufacture is the separation of "proteins of interest" – the active elements in drugs – from other materials. The primary method used is ion-exchange chromatography, which is like using a colander to separate cooked pasta from water. In this case, a separation column removes proteins from water and other cellular material. Landes said raw material containing the proteins is injected into the top of a separation column, or tube. The mixture is the "mobile phase" of the process, and it can either be pulled through the tube via gravity or pushed through.

Along the way, the liquid encounters a "stationary phase," a structure that incorporates ligands – binding ions or molecules. In theory, they capture only the proteins of interest, while the unwanted material passes through. The proteins are later washed off in a purifying step called elution. It's this stationary phase that Landes said should be tuned. That can only happen by knowing what occurs at the molecular level.

"Our fundamental understanding of this process at the level where proteins bind to ligands, which basically drives several different industries, is ridiculously small," she said. "We should take care to understand everything about separation, because up to half the cost of bringing a drug to market is for separation and purification – and the global pharmaceutical market is more than $100 billion annually. Do the math!"

The remarkable part, Landes said, is that the stochastic theory of chromatography, which describes single-molecule interactions and could improve the process, has been around for decades. But until now, nobody has had access to a tool to validate it through experimentation, especially for single proteins.

"It can actually describe and let us tune at the chemical level what's really going on in separations," she said of the theory. "But the only way to use the theory is to collect the information that describes the interaction one protein at a time."

Landes and her team, which included lead author and graduate student Lydia Kisley, postdoctoral researcher Jixin Chen, undergraduate Andrea Mansur and graduate student Bo Shuang, decided they had the way. They found that the super-resolution technique called mbPAINT they developed to identify individual sequences along strands of DNA could work equally well for other processes that involve the capture and release of single molecules, such as the proteins and ligands in chromatography.

The earlier work let them resolve structures as small as 30 nanometers – 30 billionths of a meter, at least 10 times smaller than the wavelength of light – by building up pictures over time of a probe molecule that would fluoresce when temporarily captured by the immobilized DNA.

The ability to map the location of proteins as they attach to ligands gives a much more precise look at the mechanism that makes column chromatography possible, Landes said. It also let the Rice team look at the process in a two-dimensional, rather than three-dimensional, format as they attached ligands to a film rather than a chromatography tube.

The results showed that at the molecular level, ligands embedded in the agarose-based stationary film would only capture proteins -- in this case, a synthesized peptide -- when at least three ligands were clustered together.

"Industry uses charged ligands immobilized on the surface as a hand to grab a protein flowing by," Chen said. "Once the protein encounters a ligand, their charges attract each other and they stick together. But now we can see that one single charged ligand isn't enough to grab it. It only really happens when multiple ligands are clustered in a small area and work together to grab a protein."

With the benefit of this knowledge, stationary phases in chromatography can be better engineered and optimized, Landes said. "And it's not just a charge-charge interaction," she said. "We show that there's a spatial arrangement to the ligands that's also important. We've learned that although the accepted way to improve ion-exchange is to increase the number of fingers grabbing each protein, those fingers have to be ideally organized as a hand."

She said the combination of mbPAINT and stochastic theory could work equally well to optimize point-of-care diagnostic tests that depend on the capture of analytes in a flowing fluid, in water purification columns and in catalysis for oil and gas refineries. "The field is pretty wide open, compared to the biology side," Kisley said.

Short of building and testing a chromatography device, Landes thinks the burden of proof has been met through her team's experiments. "We think up until now the chromatography tail has been wagging the dog. Now that we have the ability to match what we see to a real theory that makes physical sense, it's time to use it."

###

Co-authors of the paper included Richard Willson, the University of Houston's Huffington-Woestemeyer Professor of Chemical and Biomolecular Engineering and professor of biochemical and biophysical sciences, and his group, Wen-Hsiang Chen, a postdoctoral researcher at Texas Children's Hospital, research assistant Katerina Kourentzi and graduate students Mohan-Vivekanandan Poongavanam and Sagar Dhamane at the University of Houston. Landes is an assistant professor of chemistry and electrical and computer engineering at Rice.

Watch a video about the research at http://youtu.be/tFrpipN2ftU

When posted, the abstract will appear at http://www.pnas.org/cgi/doi/10.1073/pnas.1318405111

Follow Rice News and Media Relations via Twitter @RiceUNews

Related Materials:

Landes Research Group: http://www.lrg.rice.edu

Richard Willson: http://www.chee.uh.edu/faculty/willson

Image for download:

http://news.rice.edu/wp-content/uploads/2014/01/0121_DRUG-1-web.jpg

Rice University researchers used their super-resolution technique to pinpoint the locations of single proteins and analyze their interactions with other molecules in a study that could optimize processes critical to the pharmaceutical and other industries. From left, Rice postdoctoral researcher Jixin Chen, graduate student Lydia Kisley, undergraduate Andrea Mansur, graduate student Bo Shuang and Christy Landes, an assistant professor of chemistry and electrical and computer engineering. (Credit: The Landes Research Group/Rice University)

Located on a 300-acre forested campus in Houston, Rice University is consistently ranked among the nation's top 20 universities by U.S. News & World Report. Rice has highly respected schools of Architecture, Business, Continuing Studies, Engineering, Humanities, Music, Natural Sciences and Social Sciences and is home to the Baker Institute for Public Policy. With 3,708 undergraduates and 2,374 graduate students, Rice's undergraduate student-to-faculty ratio is 6-to-1. Its residential college system builds close-knit communities and lifelong friendships, just one reason why Rice has been ranked No. 1 for best quality of life multiple times by the Princeton Review and No. 2 for "best value" among private universities by Kiplinger's Personal Finance. To read "What they're saying about Rice," go to http://tinyurl.com/AboutRiceU.

END



ELSE PRESS RELEASES FROM THIS DATE:

Spider silk ties scientists up in knots

2014-01-23
Two years ago, researchers from Iowa State University (USA) published a study which concluded that spider silk conducts heat as well as metals. Now, a team from the University of the Basque ...

Can personalized tumor vaccines improve interleukin-2 treated metastatic melanoma?

2014-01-23
New Rochelle, NY, January 22, 2014—Metastatic melanoma has a poor prognosis, but treatment with high-dose interleukin-2 (IL2) can extend survival. Now, ...

Galaxies on FIRE: Star feedback results in less massive galaxies

2014-01-23
For decades, astrophysicists have encountered a puzzling contradiction: although many galactic-wind models—simulations of how matter is distributed in our universe—predict that the majority of ...

Cooling microprocessors with carbon nanotubes

2014-01-23
"Cool it!" That's a prime directive for microprocessor chips and a promising new solution to meeting this imperative is in the ...

UofL epidemiologist uncovers new genes linked to abdominal fat

2014-01-23
LOUISVILLE, Ky. – Excess abdominal fat can be a precursor to diseases such as cardiovascular disease, type 2 diabetes and cancer. A person's measure of belly fat is reflected in the ratio ...

Humans can use smell to detect levels of dietary fat

2014-01-23
PHILADELPHIA (January 22, 2014) – New research from the Monell Center reveals humans can use the sense of smell to detect dietary fat in food. As food smell almost always is detected before taste, the findings ...

'Watch' cites concern about femoral neck fractures in long-necked modular implants

2014-01-23
Needham, MA.–JBJS Case Connector, an online case report journal published by The Journal of Bone and Joint Surgery, has issued ...

Vulvar condition causing painful sex strikes twice as many Hispanic women

2014-01-23
ANN ARBOR, Mich. — ...

Drug discovery potential of natural microbial genomes

2014-01-23
Scientists at the University of California, San Diego have developed a new genetic platform that allows efficient production of naturally ...

Malaria drug combo could help prevent pregnancy complications in lupus patients

2014-01-23
An anti-malaria drug combination might be useful in helping to prevent pregnancy complications in women with lupus and the related disorder antiphospholipid syndrome, Yale School of Medicine ...

LAST 30 PRESS RELEASES:

Fat may play an important role in brain metabolism

New study finds no lasting impact of pandemic pet ownership on human well-being

New insights on genetic damage of some chemotherapies could guide future treatments with less harmful side effects

Gut microbes could protect us from toxic ‘forever chemicals’

Novel modelling links sea ice loss to Antarctic ice shelf calving events

Scientists can tell how fast you're aging from a single brain scan

U.S. uterine cancer incidence and mortality rates expected to significantly increase by 2050

Public take the lead in discovery of new exploding star

What are they vaping? Study reveals alarming surge in adolescent vaping of THC, CBD, and synthetic cannabinoids

ECMWF - delivering forecasts over 10 times faster and cutting energy usage by 1000

Brazilian neuroscientist reveals how viral infections transform the brain through microscopic detective work

Turning social fragmentation into action through discovering relatedness

Cheese may really be giving you nightmares, scientists find

Study reveals most common medical emergencies in schools

Breathable yet protective: Next-gen medical textiles with micro/nano networks

Frequency-engineered MXene supercapacitors enable efficient pulse charging in TENG–SC hybrid systems

Developed an AI-based classification system for facial pigmented lesions

Achieving 20% efficiency in halogen-free organic solar cells via isomeric additive-mediated sequential processing

New book Terraglossia reclaims language, Country and culture

The most effective diabetes drugs don't reach enough patients yet

Breast cancer risk in younger women may be influenced by hormone therapy

Strategies for staying smoke-free after rehab

Commentary questions the potential benefit of levothyroxine treatment of mild hypothyroidism during pregnancy

Study projects over 14 million preventable deaths by 2030 if USAID defunding continues

New study reveals 33% gap in transplant access for UK’s poorest children

Dysregulated epigenetic memory in early embryos offers new clues to the inheritance of polycystic ovary syndrome (PCOS)

IVF and IUI pregnancy rates remain stable across Europe, despite an increasing uptake of single embryo transfer

It takes a village: Chimpanzee babies do better when their moms have social connections

From lab to market: how renewable polymers could transform medicine

Striking increase in obesity observed among youth between 2011 and 2023

[Press-News.org] Better protein capture a boon for drug manufacturers
Rice University technique could widen bottleneck for pharmaceutical, other industries