Synthetic organic chemistry as a field of research may seem far removed from cancer treatment. But organic chemists like Rice University’s Julian West are constantly developing new tools to help precision-design new drugs for targeting cancer cells.

West was recruited to Rice’s department of chemistry in 2019 from the California Institute of Technology, where he was a postdoctoral fellow, with the help of a First-Time Tenure-Track Award from CPRIT.

West likens his trade to designing tools. “An effective and game-changing therapy is like a really well-built car,” he says. “Something that does exactly what you want it to do is precision-designed, but in order to get these sorts of molecules we need really precise tools to fine-tune and sculpt molecules so that they will be perfect for the job.”

Perhaps there is a therapy or drug that works reasonably well, but could be improved or made less toxic. But sometimes the ways in which scientists would like to alter the molecule just aren’t possible with known chemical reactions. West looks at these types of challenges and tries to see how he could gain a foothold, by making a molecular intermediate that’s more reactive, for example.

Read More

Synthetic organic chemistry as a field of research may seem far removed from cancer treatment. But organic chemists like Rice University’s Julian West are constantly developing new tools to help precision-design new drugs for targeting cancer cells.

West was recruited to Rice’s department of chemistry in 2019 from the California Institute of Technology, where he was a postdoctoral fellow, with the help of a First-Time Tenure-Track Award from CPRIT.

West likens his trade to designing tools. “An effective and game-changing therapy is like a really well-built car,” he says. “Something that does exactly what you want it to do is precision-designed, but in order to get these sorts of molecules we need really precise tools to fine-tune and sculpt molecules so that they will be perfect for the job.”

Perhaps there is a therapy or drug that works reasonably well, but could be improved or made less toxic. But sometimes the ways in which scientists would like to alter the molecule just aren’t possible with known chemical reactions. West looks at these types of challenges and tries to see how he could gain a foothold, by making a molecular intermediate that’s more reactive, for example.

“It’s like a mountain climber looking at a 20-foot sheer wall,” he says. Without handholds or footholds there is no obvious way to the top. “We want to figure out how to turn these insurmountable elements of molecules into more functional parts by creating a chink in the wall to add a foothold. Ultimately this helps us deliver more effective oncology molecules.”

West works not only with small drug molecules but also with large, specialized antibodies. “Antibodies are some of the most amazing biochemical macromolecules that we have because they have such incredible specificity; they are the bloodhounds of the body,” he says. Antibodies themselves essentially mark a pathogen or a cancer cell for an immune system destroyer to neutralize it. “But we’d also like to be able to hitch something else to an antibody, say a drug or a diagnostic molecule, and deliver it to a cancer cell,” he says.

One problem is that these biomolecules are huge, and the payloads are tiny. It’s a challenge to figure out how to attach two things with a monumental size difference. But this puzzle appealed to West. He saw an opportunity to develop new coupling methods for attaching small molecules to antibodies that would be efficient, robust, and compatible, and could be adapted to a wide variety of antibody/small molecule pairs.

West says he always keeps the end user in mind when developing new tools; not every scientist working in drug development is a skilled organic chemist. Working at a place like Rice has allowed him to have informative conversations not only with collaborators in his own department but also with oncology researchers and clinicians in the medical center across the street.

CPRIT’s funding was especially important for hiring curious and thoughtful people with whom to work, he says. “I saw the opportunity to grow my lab much faster than I otherwise would have been able to do, and build this multidisciplinary team to work on problems that really matter.”

West is from Edmonton, Alberta, and earned his undergraduate degree in chemistry from the University of British Columbia. He received his Ph.D. from Princeton University in organic synthesis before beginning a postdoctoral fellowship at Caltech in 2017.

Read Less