Martin Lepsik
Univ. Grenoble Alpes, CNRS, CERMAV, 38000 Grenoble, France


Felix Tobola, Martin Lepsik, Syeda Rehana Zia, Hakon Leffler, Ulf Nilsson, Ola Blixt, Anne Imberty, Birgit Wiltschi ChemBioChem 2022, 23, e202100593

Engineering the Ligand Specificity of the Human Galectin-1 by Incorporation of Tryptophan Analogues
Galectin-1 is a beta-galactoside-binding lectin with manifold biological functions. A single tryptophan residue (W68) in its carbohydrate binding site plays a major role in ligand binding and is highly conserved among galectins. To fine tune galectin-1 specificity, we introduced several non-canonical tryptophan analogues at this position of human galectin-1 and analyzed the resulting variants using glycan microarrays. Two variants containing 7-azatryptophan and 7-fluorotryptophan showed a reduced affinity for 3'-sulfated oligosaccharides. Their interaction with different ligands was further analyzed by fluorescence polarization competition assay. Using molecular modeling we provide structural clues that the change in affinities comes from modulated interactions and solvation patterns. Thus, we show that the introduction of subtle atomic mutations in the ligand binding site of galectin-1 is an attractive approach for fine-tuning its interactions with different ligands.


Compounds are: 7-azatryptophan (TRN) and 7-fluorotryptophan (TRF)

In leap file, note commands:
#modified Trp 68
bond sys.67.C sys.68.N1
bond sys.68.C4 sys.69.N

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Last modified 17 Sep 2012