Abhishek Sharma’s Lab Awarded $463K NIH Grant to Expand the Possibilities of Drug Discovery
The grant will enable the development of chemical synthesis methods to broaden the availability of molecular building blocks, ultimately providing access to more “chemical space” to develop new therapeutic agents.
Abhishek Sharma, assistant professor in the Department of Chemistry and Chemical Biology (CCB) in the Schaefer School of Engineering and Science, was recently awarded a grant of $462,600 from the National Institutes for Health. His project, entitled “ Modular Approaches to Unusual Borylated Heterocycles Using Novel Acylborons and alpha-Hydroxy Borons as Enabling Tools,” will enable him to continue one of his primary research focuses of expanding the chemical space (novel structures) of medicinally important molecules—in this case, heterocyclic drugs.
Developing new types of heterocyclic molecules and new ways to connect these heterocycles with other molecular building blocks is one of the major strategies to generating novel drugs that can tackle the challenge of drug resistance in diseases such as cancer and bacterial or viral infections. The molecular construction of a drug molecule is accomplished by connecting smaller building blocks via chemical reactions. Heterocycles that have boronate groups are one of the most commonly used building blocks to construct larger and more complex chemical structures found in drugs and natural products. Despite the remarkable progress in the synthesis and application of boron-containing molecules, there are still several challenges.
A major limitation with the currently available chemical synthesis techniques is that these methods provide access to only a very limited type of boryl heterocycles, which ultimately restricts the number of different types of drug molecules (i.e., the “chemical space” of drugs) that can be prepared as potential drugs. In other words, the chemical space of all the possible heterocycle-containing drug structures is extremely large; but current chemical synthesis methods provide access to a very small fraction of this chemical space because of the limited availability of suitable molecular building blocks.
In this research project, Sharma and his team will prepare several fundamentally novel classes of acylborons and alpha-hydroxy borons, and demonstrate their applications in preparing medicinally important and structurally novel heterocycles that would be difficult to prepare using other available methods.
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