Two-stage interaction of the tumor nursing galectin-1 with the antiangiogenic peptide anginex

Zsófia, Hegedüs [Hegedüs, Zsófia (gyógyszerkémia), author] Subsidised Research Units of the Hungarian Acad... (USZ / FP / DPhC); Edit, Wéber [Wéber, Edit (gyógyszerkémia), author] Subsidised Research Units of the Hungarian Acad... (USZ / FP / DPhC); Lea, Végh [Végh, Lea (genetika), author] Genetikai Intézet (MTA SZBK); Balázs, Váczi [Váczi, Balázs (genetika), author] Genetikai Intézet (MTA SZBK); Vilmos, Tubak [Tubak, Vilmos (biokémia), author] Genetikai Intézet (MTA SZBK); Éva, Kriston-Pál [Kriston-Pál, Éva (tumorbiológia), author] Genetikai Intézet (MTA SZBK); Zoltán, Kele [Kele, Zoltán (Kémiai analitika,...), author] Department of Medical Chemistry (USZ / ÁOK); Éva, Monostori [Monostori, Éva (Immunológia), author] Genetikai Intézet (MTA SZBK); Tamás, A. Martinek ✉ [Martinek, Tamás (Gyógyszerkémia), author] Department of Pharmaceutical Analytics (USZ / FP)

English Scientific Article (Journal Article)
  • SJR Scopus - Condensed Matter Physics: Q2
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    The 33mer peptide anginex is a potent inhibitor of angiogenesis and tumor growth. Its biological activity is dependent on the beta-galactoside-binding protein galectin-1 (gal-1), which has been reported to be the main receptor for anginex. The gal-1-anginex interaction has been observed using surface plasmon resonance and mass spectrometric methods, but the stoichiometry and affinity in the solution remain elusive. Our aim was to characterize the gal-1-anginex interaction via isothermal titration calorimetry. In order to ensure protein purity and integrity, native gel electrophoresis, Western blot analysis, mass spectrometric measurements, and ultracentrifugation were carried out for the recombinant wild-type human gal-1 and V5D gal-1 expressed in E. coli. Two stages were identified in the titration curves: (i) formation of a 4:1 galectin-1-anginex complex with low nM affinity, and (ii) a complex with 1:1 stoichiometry exhibiting K (D) > 200 nM. The 4:1 complex was robust at different concentrations, and neither the oxidation state nor the V5D mutation (a monomeric gal-1 mutant) of gal-1 affected this stoichiometry. The presence of the high-affinity 4:1 interaction may have implications for the biological applications of anginex.
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    2020-07-02 17:41