Creating new molecules underlies the development of any small-molecule therapeutic for cancer. The synthetic chemists who construct the scaffolding often have to invent new chemical methods to create novel drugs.
A chemist at Baylor University Department of Chemistry & Biochemistry is trying to incorporate inexpensive and widely available materials into the synthesis of complex cancer therapeutics. Liela Romero, an alumna of the department, was recruited in 2020 from the Massachusetts Institute of Technology, where she was a postdoctoral fellow, with a First-Time Tenure-Track Award from CPRIT.
Nature is the most efficient chemist in creating complex molecules, which are often toxins that protect the organism that produces them. These toxins may also have the ability to kill cancer cells. Cancer-killing natural products can be identified in screens, but then, scientists either have to extract the toxin from the organism or figure out how to recreate it in a lab.
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Creating new molecules underlies the development of any small-molecule therapeutic for cancer. The synthetic chemists who construct the scaffolding often have to invent new chemical methods to create novel drugs.
A chemist at Baylor University Department of Chemistry & Biochemistry is trying to incorporate inexpensive and widely available materials into the synthesis of complex cancer therapeutics. Liela Romero, an alumna of the department, was recruited in 2020 from the Massachusetts Institute of Technology, where she was a postdoctoral fellow, with a First-Time Tenure-Track Award from CPRIT.
Nature is the most efficient chemist in creating complex molecules, which are often toxins that protect the organism that produces them. These toxins may also have the ability to kill cancer cells. Cancer-killing natural products can be identified in screens, but then, scientists either have to extract the toxin from the organism or figure out how to recreate it in a lab.
Often the original natural product is produced in vanishingly small amounts, but nature’s chemical artistry can be difficult to recreate in a lab. If chemists do figure out how to synthesize the molecule, they can also tinker with it to make it more effective.
Romero plans to study small-molecule marine natural products with proven anticancer activity. One natural product she is studying was found to selectively kill cancer cells, with low toxicity to normal cells, but hadn’t been further developed because of the difficulty of obtaining or making it.
Now she is developing new chemical methods to synthesize it. “We’re not only interested in making these natural products and their derivatives, but we also want to develop new methods to access the products more efficiently,” Romero says. “Often it’s advantageous to change some of the functionality, to enhance their biological and pharmacological properties in order to augment their intended use as therapeutics.”
Romero hopes the derivatives will show promise as treatments for liver cancer by targeting a misregulated enzyme, killing cancer cells. Romero’s approach to its synthesis is two-pronged: make enough of the marine natural product and its derivatives for her collaborators to conduct assays to determine their efficacy and method of action, and at the same time develop more efficient syntheses using inexpensive building blocks.
“We’ve been really interested in harnessing hydrocarbon building blocks, like alkenes, dienes, or alkanes. These are easy to handle, inexpensive, and abundant, and represent ideal chemical building blocks,” Romero says. “We are working to develop new chemical methods to take these simple starting materials and rapidly build complex components with the features that we need. We then stitch these components together to assemble the final target molecule.”
A key part of Romero’s synthetic plan involves developing methods for synthesizing complex molecules in a particular three-dimensional spatial arrangement; a strategy that requires specialized catalysts.
“Having the support of CPRIT at the beginning stages of our research program ensures that we have what we need from the start,” Romero says. “The most critical time is the first year, setting up and establishing the research.”
She says she was excited to come back to Baylor, “because this department is so collegial and supportive, and it’s where I found my research interest,” Romero says. “Now having the opportunity to work with undergraduates feels like a great way to pay it forward. It’s hard to explain just how fulfilling it is to work in cancer research and also, I hope, inspire the next generation of scientists.”
Romero received her undergraduate training in biochemistry at Baylor, and her Ph.D. in organic chemistry from the University of Texas Southwestern Medical Center. She began a postdoctoral fellowship at MIT in 2016.
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