(Press-News.org) Scientists have developed a new method to make proteins form crystals using 'smart materials' that remember the shape and characteristics of the molecule. The technique, reported today in Proceedings of the National Academy of Sciences, should assist research into new medicines by helping scientists work out the structure of drug targets.
The process of developing a new drug normally works by identifying a protein that is involved in the disease, then designing a molecule that will interact with the protein to stimulate or block its function. In order to do this, scientists need to know the structure of the protein that they are targeting.
A technique called X-ray crystallography can be used to analyse the arrangement of atoms within a crystal of protein, but getting a protein to come out of solution and form a crystal is a major obstacle. The number of proteins identified as potential drug targets is increasing exponentially as scientists make progress in the fields of genomics and proteomics, but with current methods, scientists have successfully obtained useful crystals for less than 20 per cent of proteins that have been tried.
Now researchers at Imperial College London and the University of Surrey have developed a more effective method for making proteins crystallise using materials called 'molecularly imprinted polymers' (MIPs). MIPs are compounds made up of small units that bind together around the outside of a molecule. When the molecule is extracted, it leaves a cavity that retains its shape and has a strong affinity for the target molecule.
This property makes MIPs ideal nucleants – substances that bind protein molecules and make it easier for them to come together to form crystals. Many substances have been used as nucleants before, but none are designed specifically to attract a particular protein.
"Proteins are very comfortable in solution," said Professor Naomi Chayen, from the Department of Surgery and Cancer at Imperial College London, who led the research. "They need some convincing to come out and form a crystal.
"MIPs help this process by using the protein as a template for forming its own crystal. Once the first molecule or group of molecules is held in place, other molecules can arrange themselves around it and start to build a crystal."
In the study, Professor Chayen and her colleagues found that six different MIPs induced crystallisation of nine proteins, yielding crystals in conditions that do not give crystals otherwise. They also tested whether MIPs would be effective at producing crystals from a series of preliminary trials for three target proteins for which scientists have not previously been able to obtain crystals of sufficient quality. The presence of MIPs gave rise to crystals in eight to 10 per cent of such trials, yielding valuable crystals that would have been missed using other known nucleants.
"Rational drug design depends on knowing the structure of the protein you're trying to target, and getting good crystals is essential for studying the structure," Professor Chayen said. "With MIPs we can get better crystals than we can with other methods, and also improve the probability of getting crystals from new proteins. This is a really significant innovation that could have a major impact on research leading to the development of new drugs."
###
The research was funded by the Engineering and Physical Sciences Research Council and the European Commission.
For further information please contact:
Sam Wong
Research Media Officer
Imperial College London
Email: sam.wong@imperial.ac.uk
Tel: +44(0)20 7594 2198
Out of hours duty press officer: +44(0)7803 886 248
Notes to editors:
1. Journal reference: Saridakis et al. 'Protein crystallization facilitated by molecularly
imprinted polymers' Proceedings of the National Academy of Sciences, published online 20 June 2011.
2. The Engineering and Physical Sciences Research Council (EPSRC) is the UK's main agency for funding research in engineering and physical sciences. EPSRC invests around £800m a year in research and postgraduate training, to help the nation handle the next generation of technological change.
The areas covered range from information technology to structural engineering, and mathematics to materials science. This research forms the basis for future economic development in the UK and improvements for everyone's health, lifestyle and culture. EPSRC works alongside other Research Councils with responsibility for other areas of research. The Research Councils work collectively on issues of common concern via research Councils UK.
3. About Imperial College London
Consistently rated amongst the world's best universities, Imperial College London is a science-based institution with a reputation for excellence in teaching and research that attracts 14,000 students and 6,000 staff of the highest international quality. Innovative research at the College explores the interface between science, medicine, engineering and business, delivering practical solutions that improve quality of life and the environment - underpinned by a dynamic enterprise culture.
Since its foundation in 1907, Imperial's contributions to society have included the discovery of penicillin, the development of holography and the foundations of fibre optics. This commitment to the application of research for the benefit of all continues today, with current focuses including interdisciplinary collaborations to improve global health, tackle climate change, develop sustainable sources of energy and address security challenges.
In 2007, Imperial College London and Imperial College Healthcare NHS Trust formed the UK's first Academic Health Science Centre. This unique partnership aims to improve the quality of life of patients and populations by taking new discoveries and translating them into new therapies as quickly as possible.
Website: www.imperial.ac.uk
Twitter: www.twitter.com/imperialspark
Podcast: www.imperial.ac.uk/media/podcasts
END
New research at the University of Leicester is investigating a growing fascination with 'chav' culture among middle-class gay men in Britain.
Professor Joanna Brewis, from the University of Leicester School of Management, UK, will conduct primary empirical research into gay class tourism following publication of findings reported last year in the journal Sociology.
Research she carried out with her former colleague Professor Gavin Jack, now at La Trobe University in Australia, revealed the complex consumer patterns of middle-class homosexual men who go 'slumming' at ...
PHILADELPHIA — An international research team including University of Pennsylvania scientists has shown that the rate of sea-level rise along the U.S. Atlantic coast is greater now than at any time in the past 2,000 years and that there is a consistent link between changes in global mean surface temperature and sea level.
The research was conducted by members of the Department of Earth and Environmental Science in Penn's School of Arts and Science: Benjamin Horton, associate professor and director of the Sea Level Research Laboratory, and postdoctoral fellow Andrew Kemp, ...
The risk of developing venous thromboembolism (VTE) may be nearly twice as high for patients undergoing open surgery for colorectal problems, versus those undergoing laparoscopic colorectal (LC) resections, according to a report in the June issue of Archives of Surgery, one of the JAMA/Archives journals.
Venous thromboembolism (the formation of blood clots in the veins) occurs in up to 25 percent of patients who undergo surgery without specific steps taken to prevent the condition, according to background information in the article. The authors note that colorectal surgery ...
Most hospitals follow established practice guidelines for surgery involving Medicare beneficiaries with cancer, but in some cases their practice patterns diverge from the guidelines, according to a report published Online First today by Archives of Surgery, one of the JAMA/Archives journals.
According to background information in the article, health care quality has emerged as an important concern in the United States. However, the right care is not always delivered to the right patient at the right time, the authors remark. "Currently, it is well documented that the ...
A review of tonsillectomy-technique studies found that some new methods have advantages over traditional methods, but others are equivalent, according to a report in the June issue of Archives of Otolaryngology–Head and Neck Surgery, one of the JAMA/Archives journals.
As background information, the article states that tonsillectomy is well established in terms of safety, but is often accompanied by pain, postsurgical bleeding, and a prolonged recovery. Traditionally, the operation has been performed using cold steel and/or electrocautery dissection (CS/EC). Newer methods ...
Using a fluticasone furoate nasal spray for treatment of obstructive sleep apnea in children appears to reduce production of certain inflammatory cell proteins that may play a role in development of obstructive sleep apnea, according to a report in the June issue of Archives of Otolaryngology – Head & Neck Surgery, one of the JAMA/Archives journals.
"Obstructive sleep apnea syndrome is characterized by prolonged partial upper airway obstruction and/or intermittent complete obstruction with disruption of normal ventilation during sleep and normal sleep patterns," the authors ...
Not all varieties of botulinum toxin seem to be equally effective in reducing crow's feet wrinkles, according to a report published Online First today by Archives of Facial Plastic Surgery, one of the JAMA/Archives journals.
Botulinum toxin, a protein long considered harmful, is now known as a neuromodulator (a chemical that affects nerve impulses) that has cosmetic and medical uses, according to background information in the article. In 1989, botulinum toxin type A was approved in the United States for two muscular conditions that affect the appearance of the eyes. In ...
A newly constructed, 2,000-year history of sea level elevations will help scientists refine the models used to predict climate-change-induced sea level rise, according to an international team of climate researchers. The record also shows that the past century had the fastest recorded rate of sea level rise.
"One of the largest uncertainties in projecting the impacts of climate change involve predicting the amount and rate of future sea level rise," said Michael E. Mann, professor of meteorology, Penn State. "The societal ramifications are as great as any climate change ...
Researchers at the University of California, San Diego have developed a novel method of disguising nanoparticles as red blood cells, which will enable them to evade the body's immune system and deliver cancer-fighting drugs straight to a tumor. Their research will be published next week in the online Early Edition of the Proceedings of the National Academy of Sciences.
The method involves collecting the membrane from a red blood cell and wrapping it like a powerful camouflaging cloak around a biodegradable polymer nanoparticle stuffed with a cocktail of small molecule ...
A surprising finding in a study comparing hepatitis C virus (HCV) with hepatitis A virus (HAV) infections in chimpanzees by a team that includes scientists from the Texas Biomedical Research Institute sheds new light on the nature of the body's immune response to these viruses.
Understanding how hepatitis C becomes chronic is very important because some 200 million people worldwide and 3.2 million people in the U.S. are chronically infected with HCV and are at risk for progression to cirrhosis and liver cancer. Hepatitis C associated liver disease is the most common ...
