Chat with Carolyn R. Bertozzi

Nobel Laureate in Chemistry (2022)

About Carolyn R. Bertozzi

In the late 1990s, while others chased reactive chemical handles that disrupted living systems, Carolyn R. Bertozzi asked a deceptively simple question: what if we designed reactions that *ignored* biology entirely? Her breakthrough wasn’t just a new reaction, it was a philosophical pivot toward molecular coexistence. She coined 'bioorthogonal' to describe chemistry that proceeds reliably inside cells without interfering with native biochemistry, then engineered the first practical tools, like the Staudinger ligation and later strain-promoted azide, alkyne cycloadditions, that made real-time tracking of glycans possible for the first time. This wasn’t about labeling molecules in test tubes; it was about watching sugar coats on cancer cells change during metastasis, or visualizing inflammation in live zebrafish embryos. Her work transformed chemical biology from a reductionist discipline into a dynamic imaging science, and seeded therapeutic platforms now in clinical trials for targeted radioimmunotherapy and antibody, drug conjugates.

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Conversation Starters

Not sure where to begin? Try asking Carolyn R. Bertozzi:

  • “How did your early work on cell-surface glycans shape the design of the first bioorthogonal reaction?”
  • “What technical hurdle made the Staudinger ligation impractical for in vivo use—and how did you solve it?”
  • “Can you walk through how bioorthogonal chemistry enabled the first real-time imaging of sialic acid dynamics in tumors?”
  • “What criteria do you use to decide whether a new bioorthogonal reaction is truly 'biocompatible' beyond just being 'inert'?”

Frequently Asked Questions

Why did Bertozzi focus on glycans rather than proteins or nucleic acids when developing bioorthogonal tools?
Glycans lacked genetic templates, making them invisible to standard molecular biology tools like CRISPR or GFP tagging. Their dynamic, non-templated biosynthesis meant traditional methods couldn’t track their rapid remodeling during immune response or disease—so glycans became the ideal proving ground for chemistry that could operate where biology offered no handles.
Did Bertozzi’s Nobel Prize recognize only the invention of bioorthogonal reactions, or something broader?
The 2022 Nobel Committee explicitly honored her for ‘developing click chemistry and bioorthogonal chemistry’—but crucially, they highlighted how she ‘took click chemistry into living organisms.’ It recognized not just reaction discovery, but the conceptual leap of designing chemistry that respects biological complexity as a functional constraint, not an obstacle.
How does bioorthogonal chemistry differ fundamentally from traditional ‘click chemistry’ as defined by Sharpless?
Sharpless click chemistry prioritized high-yield, modular synthesis under controlled conditions—often organic solvents, elevated temperatures, or metal catalysts. Bioorthogonal chemistry demands selectivity *despite* water, ambient temperature, physiological pH, and competing biomolecules—requiring reactions that are both kinetically fast *and* thermodynamically silent in biological contexts.
What role did Bertozzi’s interdisciplinary lab culture play in advancing bioorthogonal applications?
Her lab deliberately merged synthetic chemists, cell biologists, and clinicians—enabling rapid iteration between probe design and functional validation. This cross-pollination led directly to applications like pretargeted PET imaging in humans and glycan-targeted ADCs now in Phase II trials, where chemical insight was continuously shaped by biological feedback.

Topics

bioorthogonal chemistrychemical biologybiochemistry

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