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Biochemistry

Sugar-transferring enzyme adds antibody to cell surface

Antibody tags along with enzyme’s natural substrate

by Celia Arnaud
December 16, 2018 | A version of this story appeared in Volume 96, Issue 49

 

Scheme showing the addition of an antibody to a cell surface by a bacterial fucosyltransferase.
Credit: Adapted from ACS Cent. Sci.
A bacterial fucosyltransferase can add antibodies to cell surfaces in a one-step reaction.

The use of live cells as therapies could become more widespread if there were easy ways to modify cell surfaces. A team led by Peng Wu of Scripps Research in California now reports a single-step chemoenzymatic reaction for attaching antibodies to cell surfaces using a bacterial fucosyltransferase enzyme from Helicobacter pylori (ACS Cent. Sci. 2018, DOI: 10.1021/acscentsci.8b00552). The researchers discovered that the enzyme can accept a broad range of substrates, so they attached an antibody to the enzyme’s normal substrate, guanosine diphosphate fucose. The enzyme successfully transfers the combination, even though it’s significantly larger than the usual substrate on its own. The reaction takes less than 10 minutes. The researchers demonstrated the method by attaching trastuzumab, an antibody used for cancer treatment, to the surface of natural killer (NK) immune cells. Trastuzumab–NK conjugates are more effective than unmodified NK cells in killing cancer cells both in cell culture and in mice. Because the fucosyltransferase tolerates such a wide range of substrates, the researchers expect that the method will be generalizable for engineering cell surfaces for research tools and medical applications.

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