Some specific cell surface receptors, such as integrins αVβ3, αVβ5 and α5β1 and the growth factor receptors VEGFRs, play a key role in the regulation of tumor angiogenesis, progression and metastasis through the formation of specific protein-protein complexes (“cross-talk”).1 The VEGFR-2/αVβ3 association has been provided in vivo;2 moreover, a dual-specific engineered protein, able to bind both VEGFR-2 and integrin αVβ3, showed a potent biological activity by blocking angiogenic processes in vitro and in vivo.3 Aiming at inhibiting both αVβ3 and VEGFR-1 receptors, the dual-specific agents 1 and 2 (FIG. 1), were synthesized conjugating the selective αVβ3/αVβ5 integrin ligand c[DKP-f3-RGD]4 and the VEGFR-1 ligand MA,5 via a copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction. The biological and conformational properties of the two conjugates are under investigation.
Synthesis of Dual-Action Ligands Targeting Both Integrin αVβ3 and VEGF Receptors / S. Zanella, M. Mingozzi, A. Dal Corso, R. Fanelli, L. Belvisi, L. Pignataro, U. Piarulli, C. Gennari. ((Intervento presentato al 39. convegno XXXIX “A. Corbella” Summer School on Organic Synthesis tenutosi a Gargnano (BS) nel 2014.
Synthesis of Dual-Action Ligands Targeting Both Integrin αVβ3 and VEGF Receptors
S. Zanella;M. Mingozzi;A. Dal Corso;L. Belvisi;C. Gennari
2014
Abstract
Some specific cell surface receptors, such as integrins αVβ3, αVβ5 and α5β1 and the growth factor receptors VEGFRs, play a key role in the regulation of tumor angiogenesis, progression and metastasis through the formation of specific protein-protein complexes (“cross-talk”).1 The VEGFR-2/αVβ3 association has been provided in vivo;2 moreover, a dual-specific engineered protein, able to bind both VEGFR-2 and integrin αVβ3, showed a potent biological activity by blocking angiogenic processes in vitro and in vivo.3 Aiming at inhibiting both αVβ3 and VEGFR-1 receptors, the dual-specific agents 1 and 2 (FIG. 1), were synthesized conjugating the selective αVβ3/αVβ5 integrin ligand c[DKP-f3-RGD]4 and the VEGFR-1 ligand MA,5 via a copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction. The biological and conformational properties of the two conjugates are under investigation.Pubblicazioni consigliate
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