New technique for identifying small molecules may speed up drug discovery, manufacturing

A UCLA-led team of scientists has developed a new technique that will enable researchers to easily and quickly determine the structures of organic molecules using very small samples. The work is already drawing significant attention in the scientific community: A preview of the paper that was posted on the website ChemRxiv was downloaded 19,000 times in 24 hours, shattering the site's previous record of 15,000 downloads in six months.

The final paper, which was published in ACS Central Science, describes a new method for using electron microscopes to examine small molecules. The approach enables scientists to analyze nanocrystals, which are so small that they can only be seen using special electron microscopes, and identify them within about 30 minutes, instead of the several hours that the current process takes.

Christopher Jones, a UCLA chemistry and biochemistry graduate student and the study's lead author, said the fact that the process works so well with "small" molecules -- those that are composed of only a few hundred atoms or less, as opposed to "large" ones, which can be made up of hundreds of thousands -- is significant because small molecules are key ingredients to the overwhelming majority of pharmaceuticals on the market today. The molecules' extra-small size allows them to more easily penetrate tightly packed cell membranes to reach their targets in the body.

In addition, Jones said, the new process can work with "vanishingly small" quantities of sample. Previously, for scientists using X-rays, the same type of information could only be gleaned from samples the size of a grain of sand. With electron microscopy, samples one-millionth or even one-billionth that size can be used.

"Using this technique, the speed at which we can formulate potentially life-saving drugs will be greatly accelerated," said Hosea Nelson, a UCLA assistant professor of chemistry and biochemistry and a senior author of the research. "It will be like going from riding a tricycle to driving a Ferrari."

Ultimately, the technique could accelerate processes for drug development because pharmaceutical companies would be able to screen more samples faster than ever before, which would reduce the time it takes to verify the molecular structure of potential drugs.

Among the words of praise from scientists and media:

  • "'Astounded,' 'blown away,' 'astonished.' Has there been another recent example in #chemistry of people going so nuts about a new advance?" Lila Guterman, deputy news editor, Science Magazine, on Twitter
  • "Very few papers in recent times have made me sit up and do a double take, but this one did. At one point the authors say they were 'astounded' by the ease of the technique, and I don't think that word is out of place at all." The Curious Wavefunction blog
  • "'I am blown away by this,' says Carolyn Bertozzi, a chemist at Stanford University. "The fact that you can get these structures from [a sample] a million times smaller than a speck of dust, that's beautiful. It's a new day in chemistry." Science Magazine
  • "To see an over-the-counter cold and flu medicine capsule being cracked open and the heterogeneous powder inside analyzed at atomic-level resolution is awesome. Even if this technique only works for a subset of organic small molecules, what is shown in these papers is stunning."UC Berkeley chemist Tom Maimone in Chemical & Engineering News
  • "Another absolutely incredible advance in #cryo-EM promises to speed our ability to determine the atomic structure of small molecules that are key to biological discovery and #drug development." National Institutes of Health Director Francis S. Collins on Twitter

"As chemists, we typically devote so much time to interpreting complex spectral data to identify our compounds," Jones said. "While developing this technique, I was amazed at how rapidly we could obtain high resolution, unambiguous chemical structures of organic molecules."

Christopher G Jones, Michael W Martynowycz, Johan Hattne, Tyler J Fulton, Brian M Stoltz, Jose A Rodriguez, Hosea M Nelson, Tamir Gonen.
The CryoEM Method MicroED as a Powerful Tool for Small Molecule Structure Determination.
ACS Cent. Sci., 2018, 4 (11), pp 1587-1592. doi: 10.1021/acscentsci.8b00760.

Most Popular Now

Novartis provides more than USD 25 million in medi…

Novartis announced that it condemns the war in Ukraine: "The continued acts of unprovoked violence are harming innocent people, and this defies our mission to improve hum...

Findings open way for personalised MS treatment

Currently available therapies to treat multiple sclerosis (MS) lack precision and can lead to serious side effects. Researchers at Karolinska Institutet in Sweden have no...

Pfizer and Biohaven's VYDURA® (rimegepant) granted…

Pfizer Inc. (NYSE: PFE) and Biohaven Pharmaceutical Holding Company Ltd. (NYSE: BHVN) today announced that the European Commission (EC) has granted marketing authorizatio...

Pfizer shares top-line results from Phase 2/3 EPIC…

Pfizer Inc. (NYSE: PFE) shared top-line results from the Phase 2/3 EPIC-PEP (Evaluation of Protease Inhibition for COVID-19 in Post-Exposure Prophylaxis) study evaluating...

A smarter way to develop new drugs

Pharmaceutical companies are using artificial intelligence to streamline the process of discovering new medicines. Machine-learning models can propose new molecules that ...

Cognitive impairment from severe COVID-19 equivale…

Cognitive impairment as a result of severe COVID-19 is similar to that sustained between 50 and 70 years of age and is the equivalent to losing 10 IQ points, say a team o...

A new toolkit to engineer safe and efficient thera…

Therapies based on engineered immune cells have recently emerged as a promising approach in the treatment of cancer. Compared to traditional drugs, engineered immune cell...

SK bioscience and GSK's adjuvanted COVID-19 vaccin…

SK bioscience and GSK announced submission of a biologics license application for SKYCovione™ a recombinant protein-based COVID-19 vaccine candidate adjuvanted with GSK’s...

Foundation S: Sanofi's new philanthropic spearhead

Sanofi today launches Foundation S - The Sanofi Collective, its philanthropic endowment fund aiming to create healthier futures for generations. Using donations, partners...

Asthma drug can block crucial SARS-CoV-2 protein

A drug used to treat asthma and allergies can bind to and block a crucial protein produced by the virus SARS-CoV-2, and reduce viral replication in human immune cells, ac...

Investigational COVID mucosal vaccine protects aga…

In animal studies that mimic human exposures, an investigational COVID vaccine designed to be taken orally not only protects the host, but also decreases the airborne spr...

Using AI to analyze large amounts of biological da…

Researchers at the University of Missouri are applying a form of artificial intelligence (AI) - previously used to analyze how National Basketball Association (NBA) playe...