UV light-induced spatial loss of sialic acid capping using a photoactivatable sialyltransferase inhibitor

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Sialic acids cap glycans displayed on mammalian glycoproteins and glycolipids and mediate many glycan-receptor interactions. Sialoglycans play a role in diseases such as cancer and infections where they facilitate immune evasion and metastasis or serve as cellular receptors for viruses, respectively. Strategies that specifically interfere with cellular sialoglycan biosynthesis, such as sialic acid mimetics that act as metabolic sialyltransferase inhibitors, enable research into the diverse biological functions of sialoglycans. Sialylation inhibitors are also emerging as potential therapeutics for cancer, infection, and other diseases. However, sialoglycans serve many important biological functions and systemic inhibition of sialoglycan biosynthesis can have adverse effects. To enable local and inducible inhibition of sialylation, we have synthesized and characterized a caged sialyltransferase inhibitor that can be selectively activated with UV-light. A photolabile protecting group was conjugated to a known sialyltransferase inhibitor (P-SiaFNEtoc). This yielded a photoactivatable inhibitor, UV-SiaFNEtoc, that remained inactive in human cell cultures and was readily activated through radiation with 365 nm UV light. Direct and short radiation of a human embryonic kidney (HEK293) cell monolayer was well-tolerated and resulted in photoactivation of the inhibitor and subsequent spatial restricted synthesis of asialoglycans. The developed photocaged sialic acid mimetic holds the potential to locally hinder the synthesis of sialoglycans through focused treatment with UV light and may be applied to bypass the adverse effects related to systemic loss of sialylation.

OriginalsprogEngelsk
TidsskriftRSC Chemical Biology
Vol/bind4
Udgave nummer7
Sider (fra-til)506-511
Antal sider6
DOI
StatusUdgivet - 2023

Bibliografisk note

Funding Information:
The authors thank dr. H. Elemans for supplying the UV light sources and L. van der Krabben for helping with the UV light energy measurements. This work was supported by grants from the European Commission (GlycoSkin H2020-ERC, 772735-2 to H. H. W., and ERC-Stg GlycoEdit, 758913 and MSCA-ITN-2020 grant Glytunes, 956758 to T. J. B), the Lundbeck Foundation and Novo Nordisk Foundation to H. C., and a Dutch Research Council (NWO) Veni grant to C. B. (VI.Veni.202.045).

Publisher Copyright:
© 2023 RSC.

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