Chemists at Cold Spring Harbor Laboratory (CSHL) created a new collection of molecular compounds and began testing them as potential leads in the search for new drugs. Among these molecules, they found several that are promising for the development of antibiotics and cancer treatment. Sound like a eureka moment? Good ranking. But this is more of an example of hard chemistry done simply.

The new compounds were synthesized using a new, efficient way of linking molecules together, developed in the laboratory of CSHL professor John Moses. Moses calls his innovative process Accelerated SuFEx Click Chemistry (ASCC). This is one of the latest advances in the Nobel Prize-winning field of click chemistry, pioneered by Moses K.’s mentor, Barry Sharpless.

Click chemistry rapidly connects molecules together, forming new complex structures. This allows drug developers to collect large numbers of compounds for further research. Click chemistry with accelerated SuFEx can produce more compounds in fewer steps and higher yields.

“If you can make molecules, you can test them,” Moses explains. “And with this technology, you can do these things quickly.”

Moses and his team used ASCC to create more than 150 different new compounds, including derivatives of complex natural molecules. In the past, creating and purifying this range of molecules could take months. Musa and his team prepared these in a few days. They then tested these new molecules on cancer cells and drug-resistant strains of bacteria.

In a series of experiments, Joshua Homer, a researcher in Moses’ laboratory, synthesized a series of molecules similar to the anticancer compound called combretastatin A4. Homer discovered that two of the new molecules could kill cancer cells that normally resist standard chemotherapy. These molecules may one day be the solution to the treatment of hard-to-treat breast and pancreatic cancers.

Researchers have also created antibiotic-like molecules called dapsone. They found that some of these molecules were effective against dapsone-resistant bacteria. Homer says ASCC could help chemists redesign other complex antibiotics to overcome hardened pathogen defenses.

Looking ahead, Moses and his team will continue to use ASCC to explore new horizons in drug discovery and fine-tune potential drug candidates. In the meantime, they hope other researchers will apply the Accelerated SuFEx technology to their own drug discovery platforms.

Summarizing the benefits of ASCC, Moses says: “It’s just a way of finding function. You can always improve and optimize things. But let’s achieve this as soon as possible. I hope we can speed up the whole process.”