Nodal is a growth factor expressed during early embryonic development, but reactivated in several advanced-stage cancers. Targeting of Nodal signaling, which occurs via the binding to Cripto-1 co-receptor, results in inhibition of cell aggressiveness and reduced tumor growth. The Nodal binding region to Cripto-1 was identified and targeted with a high affinity monoclonal antibody (3D1). By STD-NMR technique, we investigated the interaction of Nodal fragments with 3D1 with the aim to elucidate at atomic level the interaction surface. Data indicate with high accuracy the antibody-antigen contact atoms and confirm the information previously obtained by immune-enzymatic methods. Main residues contacted by 3D1 are P46, V47, E49 and E50, which belong to the Nodal loop involved in the interaction with the co-receptor.

Structural insights into the interaction of a monoclonal antibody and Nodal peptides by STD-NMR spectroscopy / Calvanese, Luisa; Focà, Annalia; Sandomenico, Annamaria; Focà, Giuseppina; Caporale, Andrea; Doti, Nunzianna; Iaccarino, Emanuela; Leonardi, Antonio; D'Auria, Gabriella; Ruvo, Menotti; Falcigno, Lucia. - In: BIOORGANIC & MEDICINAL CHEMISTRY. - ISSN 0968-0896. - 25:24(2017), pp. 6589-6596. [10.1016/j.bmc.2017.10.036]

Structural insights into the interaction of a monoclonal antibody and Nodal peptides by STD-NMR spectroscopy

Calvanese, Luisa
Primo
;
Caporale, Andrea;Leonardi, Antonio;D'Auria, Gabriella;Falcigno, Lucia
Ultimo
2017

Abstract

Nodal is a growth factor expressed during early embryonic development, but reactivated in several advanced-stage cancers. Targeting of Nodal signaling, which occurs via the binding to Cripto-1 co-receptor, results in inhibition of cell aggressiveness and reduced tumor growth. The Nodal binding region to Cripto-1 was identified and targeted with a high affinity monoclonal antibody (3D1). By STD-NMR technique, we investigated the interaction of Nodal fragments with 3D1 with the aim to elucidate at atomic level the interaction surface. Data indicate with high accuracy the antibody-antigen contact atoms and confirm the information previously obtained by immune-enzymatic methods. Main residues contacted by 3D1 are P46, V47, E49 and E50, which belong to the Nodal loop involved in the interaction with the co-receptor.
2017
Structural insights into the interaction of a monoclonal antibody and Nodal peptides by STD-NMR spectroscopy / Calvanese, Luisa; Focà, Annalia; Sandomenico, Annamaria; Focà, Giuseppina; Caporale, Andrea; Doti, Nunzianna; Iaccarino, Emanuela; Leonardi, Antonio; D'Auria, Gabriella; Ruvo, Menotti; Falcigno, Lucia. - In: BIOORGANIC & MEDICINAL CHEMISTRY. - ISSN 0968-0896. - 25:24(2017), pp. 6589-6596. [10.1016/j.bmc.2017.10.036]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/695330
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