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RK, the first scorpion peptide with dual disintegrin activity on α1β1 and αvβ3 integrins

Abstract : the first scorpion peptide with dual disintegrin activity on α1β1 and αvβ3 integrins. Abstract: Scorpion peptides are well known for their pharmaceutical potential on different targets. These include mainly the ion channels which were found to be highly expressed in many diseases, including cancer, auto-immune pathologies and Alzheimer. So far, however, the disintegrin activity had only been characterized for snake venom molecules. Herein, we present the first short peptide, purified from the venom of Buthus occitanus tunetanus, (termed RK) able to inhibit the cell adhesion of Glioblastoma, Melanoma and Rat pheochromocytoma to different extracellular matrix (ECM) receptors. Anti-integrin antibody assay suggests that RK interacts with both α1β1 and αvβ3 with a more pronounced effect for the former. The examination of the primary structure of RK suggests the involvement of two motifs: KSS, analogue to KTS which was characterized for α1β1 Snake venom disintegrins, and ECD, analogue to RGD which was found to be active on αvβ3. To assess their roles in the disintegrin activity of RK, we conducted a computational analysis. The molecular docking study shows that RK involves mainly two segments to interact with the α1β1 integrin, but the peptide does not implicate the KSS motif in the interaction. The molecular modeling study, suggests the key contribution of the ECD segment in the interaction with αvβ3 integrin.
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Submitted on : Friday, February 1, 2019 - 1:53:23 PM
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Oussema Khamessi, Hazem Ben Mabrouk, Houcemeddine Othman, Rym Elfessi-Magouri, Michel de Waard, et al.. RK, the first scorpion peptide with dual disintegrin activity on α1β1 and αvβ3 integrins. International Journal of Biological Macromolecules, Elsevier, 2018, 120 (B), pp.1777-1788. ⟨10.1016/j.ijbiomac.2018.09.180⟩. ⟨pasteur-02003807⟩

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