Issue 11, 2023

Glycomimetics for the inhibition and modulation of lectins

Abstract

Carbohydrates are essential mediators of many processes in health and disease. They regulate self-/non-self- discrimination, are key elements of cellular communication, cancer, infection and inflammation, and determine protein folding, function and life-times. Moreover, they are integral to the cellular envelope for microorganisms and participate in biofilm formation. These diverse functions of carbohydrates are mediated by carbohydrate-binding proteins, lectins, and the more the knowledge about the biology of these proteins is advancing, the more interfering with carbohydrate recognition becomes a viable option for the development of novel therapeutics. In this respect, small molecules mimicking this recognition process become more and more available either as tools for fostering our basic understanding of glycobiology or as therapeutics. In this review, we outline the general design principles of glycomimetic inhibitors (Section 2). This section is then followed by highlighting three approaches to interfere with lectin function, i.e. with carbohydrate-derived glycomimetics (Section 3.1), novel glycomimetic scaffolds (Section 3.2) and allosteric modulators (Section 3.3). We summarize recent advances in design and application of glycomimetics for various classes of lectins of mammalian, viral and bacterial origin. Besides highlighting design principles in general, we showcase defined cases in which glycomimetics have been advanced to clinical trials or marketed. Additionally, emerging applications of glycomimetics for targeted protein degradation and targeted delivery purposes are reviewed in Section 4.

Graphical abstract: Glycomimetics for the inhibition and modulation of lectins

Article information

Article type
Review Article
Submitted
15 noy 2022
First published
26 may 2023
This article is Open Access
Creative Commons BY license

Chem. Soc. Rev., 2023,52, 3663-3740

Glycomimetics for the inhibition and modulation of lectins

S. Leusmann, P. Ménová, E. Shanin, A. Titz and C. Rademacher, Chem. Soc. Rev., 2023, 52, 3663 DOI: 10.1039/D2CS00954D

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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