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

Top 20 breaking World Pharma News of 2018

World Pharma News proudly presents the top 20 most popular breaking news from 2018. Have a wonderful 2019 New(s) Year filled with health, happiness, and spectacular succe...

FDA approves first treatment for rare blood diseas…

The U.S. Food and Drug Administration today approved Elzonris (tagraxofusp-erzs) infusion for the treatment of blastic plasmacytoid dendritic cell neoplasm (BPDCN) in adu...

Bristol-Myers Squibb to acquire Celgene to create …

Bristol-Myers Squibb Company (NYSE:BMY) and Celgene Corporation (NASDAQ:CELG) today announced that they have entered into a definitive merger agreement under which Bristo...

Lynparza meets primary endpoint in Phase III SOLO-…

AstraZeneca and Merck & Co., Inc., Kenilworth, N.J., US (Merck: known as MSD outside the US and Canada) announced positive results from the randomised, open-label, contro...

Pediatric leukemia 'super drug' could be developed…

Northwestern Medicine scientists have discovered two successful therapies that slowed the progression of pediatric leukemia in mice, according to three studies published ...

Researchers uncover new mechanism of gene regulati…

Genes contain all the information needed for the functioning of cells, tissues, and organs in our body. Gene expression, meaning when and how are the genes being read and...

Tumors backfire on chemotherapy

Some patients with breast cancer receive chemotherapy before the tumor is removed with surgery. This approach, called 'neoadjuvant' therapy, helps to reduce the size of t...

AstraZeneca announces organisational changes

AstraZeneca is today announcing organisational changes to support continued scientific innovation and commercial success in the main therapy areas as the Company enters a...

Sandoz and Pear Therapeutics announce US launch of…

Sandoz Inc., a Novartis division, and Pear Therapeutics, Inc., announced today the US commercial launch of reSET-O(TM) for patients with Opioid Use Disorder (OUD). reSET-...

Stopping cancer from recruiting immune system doub…

Cancerous tumors trick myeloid cells, an important part of the immune system, into perceiving them as a damaged part of the body; the tumors actually put myeloid cells to...

Boehringer Ingelheim initiates a collaborative par…

Science 37, an industry leader in virtual clinical trials, and Boehringer Ingelheim announced a technology enterprise collaboration agreement that will support Boehringer...

Pfizer initiates phase 2b/3 clinical trial for PF-…

Pfizer Inc. (NYSE: PFE) announced the initiation of a Phase 2b/3 clinical trial for its oral JAK3 inhibitor, PF-06651600, for the treatment of patients with moderate to s...