Galectin-1 (Gal-1), a ubiquitous P-galactoside-binding protein expressed by various
normal and pathological tissues, has been implicated in cancer and autoimmune/inflammatory
diseases in consequence of its regulatory role in adhesion, cell viability, proliferation,
and angiogenesis. The functions of Gal-1 depend on its affinity for P-galactoside-containing
glycoconjugates; accordingly, the inhibition of sugar binding blocks its functions,
hence promising potential therapeutic tools. The Tyr-Xxx-Tyr peptide motifs have been
reported to be glycomimetic sequences, mainly on the basis of their inhibitory effect
on the Gal-1-asialofetuin (ASF) interaction. However, the results regarding the efficacy
of the Tyr-Xxx-Tyr motif as a glycomimetic inhibitor are still controversial. The
present STD and trNOE NMR experiments reveal that the Tyr-Xxx-Tyr peptides studied
do not bind to Gal-1, whereas their binding to ASF is clearly detected. N-15,H-1 HSQC
titrations with N-15-labeled Gal-1 confirm the absence of any peptide-Gal-1 interaction.
These data indicate that the Tyr-Xxx-Tyr peptides tested in this work are not glycomimetics
as they interact with ASF via an unrevealed molecular linkage.
