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, LuisaPrimo
;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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.