QS-21 is a promising adjuvant which improves the performance of certain drugs. The trouble is, QS-21 is derived from an evergreen tree (Quillaja saponari) found in limited locations in Chile. It also has some other qualities that limit vaccine effectiveness.
Researchers at Memorial Sloan Kettering Cancer Center (MSKCC) in New York have been working on a synthetic version of QS-21. As Chemical & Engineering News reported this week:
Now, the Gin/Tan group and those of Philip O. Livingston, Govind Ragupathi, and Jason S. Lewis at MSKCC have created a greatly simplified QS-21 analog that is more synthetically accessible and less toxic than the natural product (Nat. Chem. 2014, DOI: 10.1038/nchem.1963). They have also uncovered new details on QS-21’s poorly understood mechanism of action.
The team plans to commercialize such semisynthetic QS-21 variants as adjuvants through Adjuvance Technologies, a company Gin started with Livingston and Ragupathi.
The researchers created the analog from QS-21 by deleting a branched trisaccharide and an additional sugar and simplifying an acyl chain, among other structural changes. The analog retains QS-21’s full activity while lowering its toxicity.
“I would never have expected that one could strip down this beast of a molecule to this extent and still retain activity, much less have reduced toxicity,” comments Jeffrey C. Gildersleeve, head of chemical glycobiology at the National Cancer Institute and winner of the ACS Division of Carbohydrate Chemistry’s 2011 David Y. Gin New Investigator Award….
I am not a chemist, yet I find the process of innovation key in all fields. My brother-in-law, Dr. David Gin, passed away in 2011, while working on this ground-breaking research few of us understood. This innovation has the potential to improve the functioning of important vaccines, while preventing unnecessary impacts on forests in South America. And who among us would not want our work to carry on beyond our own lives, especially with the potential to save so many others.
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Disclosure: While I have no direct financial interest in Adjuvance Technologies or this research, I do serve as a trustee for a trust with interests.
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