In 2022 Carolyn Bertozzi shared the Nobel Prize in Chemistry with Barry Sharpless and Morten Meldal for discovery of click chemistry. Bertozzi invented a biorthogonal variation of Sharpless and Meldal reactions. In this paper the authors described a novel way of manipulating the click chemistry reaction, which includes a ligation reaction modeled after the Staudinger reaction that forms two reactive partners which are abiotic and chemically orthogonal to native cellular components. In essence this transformation permitted its execution within the cell’s interior, offering new ways to investigate and follow intracellular interactions. This reaction contributed to more targeted cancer treatments and other pharmaceutical applications.

(Thanks to Juan Weiss for this reference and its interpretation.)

The authors applied click chemistry to previously inaccessible biologic
environments. Towards that end, they used a modified azide and clicking it onto an alkyne but without using copper ions which are toxic to cells, they invent a reaction between azides and alkynes that reacts in a vigorous manner and totally without the help of copper. With this they invent a copper free click reaction called the “strain-promoted alkyne-azide cycloaddition’ or the ‘SPAAC’ reaction. By adding fluorophores (see Green Fluorescent Protein GM- 13564) to the reaction platform, they could
illuminate glycans in the cell surface and the emerging glycome of the zebrafish.

Order of authorship in the original publication: Laughlin, Baskin, et al, Bertozzi.

(Thanks to Juan Weiss for this reference and its interpretation.)