Issue 25, 2024

Anticancer approach by targeted activation of a global inhibitor of sialyltransferases with acrolein

Abstract

Cells are covered with a thick layer of sugar molecules known as glycans. Abnormal glycosylation is a hallmark of cancer, and hypersialylation increases tumor metastasis by promoting immune evasion and inducing tumor cell invasion and migration. Inhibiting sialylation is thus a potential anticancer treatment strategy. However, targeting sialic acids is difficult because of the lack of selective delivery tools. Here, we present a prodrug strategy for selectively releasing the global inhibitor of sialylation peracetylated 3Fax-Neu5Ac (PFN) in cancer cells using the reaction between phenyl azide and endogenous acrolein, which is overproduced in most cancer cells. The prodrug significantly suppressed tumor growth in mice as effectively as PFN without causing kidney dysfunction, which is associated with PFN. The use of sialylated glycans as immune checkpoints is gaining increasing attention, and the proposed method for precisely targeting aberrant sialylation provides a novel avenue for expanding current cancer treatments.

Graphical abstract: Anticancer approach by targeted activation of a global inhibitor of sialyltransferases with acrolein

Supplementary files

Article information

Article type
Edge Article
Submitted
09 Feb 2024
Accepted
28 Apr 2024
First published
24 May 2024
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY-NC license

Chem. Sci., 2024,15, 9566-9573

Anticancer approach by targeted activation of a global inhibitor of sialyltransferases with acrolein

T. Kasahara, T. Chang, H. Yoshioka, S. Urano, Y. Egawa, M. Inoue, T. Tahara, K. Morimoto, A. R. Pradipta and K. Tanaka, Chem. Sci., 2024, 15, 9566 DOI: 10.1039/D4SC00969J

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