Using atomic-force microscopy to find new meds

European scientists are the first to use an atomic-force microscope to "see" the unknown molecular structure of a marine compound taken from the deepest place on Earth.

Kaiko, a remotely operated underwater vehicle built by the Japan Agency for Marine-Earth Science and Technology (JAMSTEC), retrieved the Mariana Trench samples. JAMSTEC

Scientists at the University of Aberdeen in the U.K. and IBM Research in Zurich say they are the first to use atomic-force microscopy to "see" the unknown molecular structure of a marine compound taken from the deepest place on Earth, a result that could speed up the development of new medicines.

In doing so, researchers discovered that the pressure-tolerant bacterium sampled from the deepest place on the planet--the Pacific Ocean's Mariana Trench, 35,814 feet below sea level--contains the molecular structure cephalandole A, which was originally isolated from a Taiwanese orchid.

The group's findings appear online August 1 in the journal Nature Chemistry.

A low-pass filtered three-dimensional representation of the unknown compound. Nature Chemistry

Marcel Jaspars, director of the Marine Biodiscovery Centre at the University of Aberdeen, says in a news release that being able to see a compound's molecular structure so quickly is a major step toward determining whether previously unknown compounds have medicinal properties:

The Earth's natural environment is rich with a diverse range of unique organisms from which a vast array of chemical compounds can be sourced, many of which are entirely unknown to science. These compounds have the potential to be used in the development of pharmaceuticals and other novel biomedical products. But in order to harness this potential we must first understand these compounds in terms of their molecular structure in order to determine whether they are viable for use in medicine.

It is of course long understood that natural chemical compounds--both known and still undiscovered (in caves, oceans, deserts, etc.)--have potential medicinal properties. Scientists at Aberdeen have been looking to the deep seas in the hopes of finding yet unknown chemical compounds that could be used to treat cancer, infection, inflammation, parasitic diseases, and more.

When they identified the chemical composition of their Mariana Trench sample (a bacterium called Dermacoccus abyssi) using hi-res mass spectrometry, they still needed a way to determine its precise molecular structure.

Because of the small number of protons and the positioning of certain atoms, even state-of-the-art nuclear magnetic resonance techniques were unable to determine which of four potential structures this sample had. One way to determine the structure was to take a chemical synthesis of each proposed structure, a complex task that could take months.

Instead, they asked the team at IBM in Zurich to use noncontact atomic-force microscopy to image individual molecules with atomic resolution. Using density functional theory calculations, they confirmed within one week the structure to be cephalandole A. As the group puts it, the microscope enabled them to "see" the structure, and to see it fast.

"Determining the structure of an unknown compound is a time-consuming process which could take months, therefore the ability to immediately 'see' the structure of a chemical compound simply by looking through a microscope is a tremendous feat," Jaspars says. "This new approach could lead to much faster identification of unknown compounds and ultimately speed up the process of the development of new medicines."

 

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