Galectin-1-asialofetuin interaction is inhibited by peptides containing the tyr-xxx-tyr motif acting on the glycoprotein.
Galectin-1 (Gal-1), a ubiquitous beta-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 beta-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. (15)N,(1)H HSQC titrations with (15)N-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.
Wéber
Edit
E
Institute of Pharmaceutical Chemistry, University of Szeged, Eötvös u. 6, 6720 Szeged, Hungary.
Hetényi
Anasztázia
A
Váczi
Balázs
B
Szolnoki
Eva
E
Fajka-Boja
Roberta
R
Tubak
Vilmos
V
Monostori
Eva
E
Martinek
Tamás A
TA
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001212:Asialoglycoproteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D060748:Fetuins; D037483:Galectin 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D009682:Magnetic Resonance Spectroscopy; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011485:Protein Binding; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D014443:Tyrosine / Q000737:chemistry*; D000509:alpha-Fetoproteins / Q000037:antagonists & inhibitors / Q000378:metabolism*
D001212:Asialoglycoproteins; D060748:Fetuins; D037483:Galectin 1; D006023:Glycoproteins; D010455:Peptides; D011994:Recombinant Proteins; D000509:alpha-Fetoproteins; C017029:asialofetuin; D014443:Tyrosine