Glycocalix[4]arenes and their affinity to a library of galectins: the linker matters
Galectins are lectins that bind β-galactosides. They are involved in important extra- and intracellular biological processes such as apoptosis, and regulation of the immune system or the cell cycle. High-affinity ligands of galectins may introduce new therapeutic approaches or become new tools for b...
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Published in | Organic & biomolecular chemistry Vol. 21; no. 6; pp. 1294 - 132 |
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Main Authors | , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
CAMBRIDGE
Royal Soc Chemistry
08.02.2023
Royal Society of Chemistry |
Subjects | |
Online Access | Get full text |
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Summary: | Galectins are lectins that bind β-galactosides. They are involved in important extra- and intracellular biological processes such as apoptosis, and regulation of the immune system or the cell cycle. High-affinity ligands of galectins may introduce new therapeutic approaches or become new tools for biomedical research. One way of increasing the low affinity of β-galactoside ligands to galectins is their multivalent presentation,
e.g.
, using calixarenes. We report on the synthesis of glycocalix[4]arenes in
cone
,
partial cone
,
1,2-alternate
, and
1,3-alternate
conformations carrying a lactosyl ligand on three different linkers. The affinity of the prepared compounds to a library of human galectins was determined using competitive ELISA assay and biolayer interferometry. Structure-affinity relationships regarding the influence of the linker and the core structure were formulated. Substantial differences were found between various linker lengths and the position of the triazole unit. The formation of supramolecular clusters was detected by atomic force microscopy. The present work gives a systematic insight into prospective galectin ligands based on the calix[4]arene core.
Glycocalix[4]arene ligands were prepared that had nanomolar affinity to galectins and induced their supramolecular aggregation. Lactose linkers and core conformations differed in their effect on galectin binding. |
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Bibliography: | https://doi.org/10.1039/d2ob02235d Electronic supplementary information (ESI) available. See DOI ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1477-0520 1477-0539 |
DOI: | 10.1039/d2ob02235d |