Health & Medicine, UK (Commonwealth Union) – A potent anti-cancer therapy has been formed with the application of “click chemistry”, in a new study conducted by the University College London (UCL) and Stanford University researchers.
Click chemistry is a term coined by chemist K. Barry Sharpless in the 2000s to describe a set of principles for the design and synthesis of molecules in a highly selective and efficient manner. Click chemistry focuses on the rapid and reliable formation of chemical bonds under mild reaction conditions. This concept has been particularly influential in the field of chemical biology, drug discovery, and materials science.
Published in the journal Nature Chemistry, this study unveils novel avenues for the potential construction of advanced cancer immunotherapies in the future.
The research group devised a tripartite anti-cancer treatment comprising three essential elements: one aimed at the cancer cell, another enlisting the assistance of a T cell, a type of white blood cell, to launch an attack on the cancerous cell, and a third component that incapacitates a portion of the cancer cell’s defensive mechanisms.
Previously, the development of such intricate three-part therapies necessitated a convoluted procedure known as protein engineering. This method involves the amalgamation of DNA sequences coding for multiple proteins, which are then inserted into a solitary cell.
Among the three-component therapies synthesized by the scientists, a notable achievement involved the utilization of an enzyme called sialidase. This enzyme effectively dismantled the sugars exploited by cancer cells to shield themselves. Remarkably, this particular therapy exhibited potent efficacy in eradicating breast cancer cells within a controlled environment. The researchers emphasized that this success underscores the burgeoning potential of the recently explored enzyme in the realm of cancer research, suggesting it could serve as a foundational element for the development of next-generation anti-cancer agents.
Dr. Peter Szijj, the lead author from UCL Chemistry, indicated that Click chemistry offers a swifter and more adaptable route for constructing these versatile anti-cancer agents compared to protein engineering. Attaching click ‘handles’ to proteins is relatively straightforward, enabling rapid exploration of numerous combinations to identify the most effective ones. In contrast, protein engineering necessitates distinct mechanisms for each component.
Professor Vijay Chudasama, the senior corresponding author from UCL Chemistry, indicated that due to the large and intricate nature of proteins, a combination of precise protein modification and dependable click chemistry is essential for their controlled fusion. The team has successfully achieved this feat, demonstrating that their approach presents a compelling alternative to the conventional method of protein engineering.
“We hope that by using chemistry to create novel and highly sophisticated multi-protein anti-cancer agents we can inspire chemists to cross the typical boundaries of the discipline to engage in novel applications in areas such as medical imaging, diagnostics and disease therapies.”
The recipients of the 2022 Nobel Prize in Chemistry were the trailblazers in the field of click chemistry. Among them, Carolyn Bertozzi, the Anne T. and Robert M. Bass Professor in the Stanford School of Humanities and Sciences and a co-author of this recent study, emerged as one of the triumphant figures. She earned this distinction for her groundbreaking contributions to biorthogonal chemistry, specifically in the realm of click chemistry within living cells.
“This new construct that brings an enzyme building block into the CiTE format has potential as a new modality for cancer immune therapy,” explained Professor Bertozzi.
Incorporating a fourth molecule, biotin, into the mix, the scientists enabled a visualization of the binding effectiveness between the components and their designated targets. They noted that this biotin molecule could be replaced by another small molecule serving a distinct purpose. For instance, it could act to minimize unwanted effects by concealing the protein structure until it specifically reaches its intended destination: the cancerous site. Within the paper, the researchers highlighted the remarkable potential that harnessing chemistry in this manner holds for crafting cancer treatments, which they believe remains largely unexplored.
