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

Pfizer and BioNTech receive positive CHMP opinion …

Pfizer Inc. (NYSE: PFE) and BioNTech SE (Nasdaq: BNTX) announced a booster dose of their Omicron BA.4/BA.5-adapted bivalent COVID-19 vaccine (COMIRNATY® Original/Omicron ...

Vividion Therapeutics names Jenna Goldberg as Chie…

Vividion Therapeutics, Inc., a biopharmaceutical company utilizing novel discovery technologies to unlock high value, traditionally undruggable targets with precision the...

Bayer with continued strong performance

The Bayer Group maintained its strong business performance across all three divisions in the third quarter. "Despite rising inflation and global supply chain problems, we...

Sanofi and GSK's next-generation COVID-19 booster …

After the European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion for VidPrevtyn® Beta, the vaccine was approved by t...

GSK announces positive Phase IIa study results for…

GSK plc (LSE/NYSE: GSK) announced positive results from a Phase IIa study demonstrating that GSK3036656, a first-in-class investigational antitubercular agent, was well t...

Sugar molecules as a target in cancer therapy

Cancer cells use sugar molecules on their surface to disable attacks by the body's immune system. Researchers at the University of Basel now report on how this mechanism ...

COVID vaccination improves effectiveness of cancer…

Patients with nasopharyngeal cancer are often treated with drugs that activate their immune system against the tumor. Until now, it was feared that vaccination against Co...

Making melanoma immortal: Pitt scientists discover…

Scientists at the University of Pittsburgh School of Medicine have discovered the missing puzzle piece in the mystery of how melanoma tumors control their mortality. I...

Unusual type of antibody shows ultrapotent activit…

An unusual type of antibody that even at miniscule levels neutralizes the Zika virus and renders the virus infection undetectable in preclinical models has been identifie...

New drug shows promise for fighting both COVID-19 …

While vaccination can provide life-saving protection against COVID-19, scientists are still searching for ways to treat severe infections, including in people who cannot ...

Machine learning can help predict patient response…

Predicting which patients will respond well to treatment is a quandary that has plagued the field of cancer immunotherapy for more than four decades. Now, researchers at ...

Study reveals vaccine confidence declined consider…

A new study suggests that, despite the success of the COVID-19 vaccination campaigns, vaccine confidence has declined significantly since the start of the pandemic. Re...