Discovery of indole-modified aptamers for highly specific recognition of protein glycoforms

Glycosylation is an abundant form of post-translational modification. Here the authors present a generalizable workflow for the selection of indole-modified aptamers that can recognize protein glycoforms with high specificity. Glycosylation is one of the most abundant forms of post-translational modification, and can have a profound impact on a wide range of biological processes and diseases. Unfortunately, efforts to characterize the biological function of such modifications have been greatly hampered by the lack of affinity reagents that can differentiate protein glycoforms with robust affinity and specificity. In this work, we use a fluorescence-activated cell sorting (FACS)-based approach to generate and screen aptamers with indole-modified bases, which are capable of recognizing and differentiating between specific protein glycoforms. Using this approach, we were able to select base-modified aptamers that exhibit strong selectivity for specific glycoforms of two different proteins. These aptamers can discriminate between molecules that differ only in their glycan modifications, and can also be used to label glycoproteins on the surface of cultured cells. We believe our strategy should offer a generally-applicable approach for developing useful reagents for glycobiology research.

Automated summary

Glycosylation is a common post-translational modification with significant impact on biological processes and diseases. The authors present a generalizable workflow for selecting aptamers with indole-modified bases to recognize specific protein glycoforms. This approach allows for the identification of aptamers with strong selectivity for specific glycoforms and offers a promising strategy for glycobiology research.