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

Authors
  • Calvanese, Luisa1
  • Focà, Annalia2
  • Sandomenico, Annamaria3
  • Focà, Giuseppina2
  • Caporale, Andrea1
  • Doti, Nunzianna2
  • Iaccarino, Emanuela4
  • Leonardi, Antonio5
  • D'Auria, Gabriella6
  • Ruvo, Menotti7
  • Falcigno, Lucia8
  • 1 CIRPeB, University of Naples Federico II, via Mezzocannone, 16, 80134 Napoli, Italy. , (Italy)
  • 2 Institute of Biostructures and Bioimaging, National Research Council, IBB-CNR, via Mezzocannone, 16, 80134 Napoli, Italy. , (Italy)
  • 3 CIRPeB, University of Naples Federico II, via Mezzocannone, 16, 80134 Napoli, Italy; Institute of Biostructures and Bioimaging, National Research Council, IBB-CNR, via Mezzocannone, 16, 80134 Napoli, Italy. , (Italy)
  • 4 DISTABIF, Università degli Studi della Campania "Lugi Vanvitelli", via Vivaldi, 43, 80100 Caserta, Italy. , (Italy)
  • 5 Dept. Medicina Molecolare e Biotecnologie Mediche, Università Federico II di Napoli, Naples, Italy. , (Italy)
  • 6 CIRPeB, University of Naples Federico II, via Mezzocannone, 16, 80134 Napoli, Italy; Institute of Biostructures and Bioimaging, National Research Council, IBB-CNR, via Mezzocannone, 16, 80134 Napoli, Italy; Dept. of Pharmacy, University of Naples Federico II, via Mezzocannone, 16, 80134 Napoli, Italy. , (Italy)
  • 7 CIRPeB, University of Naples Federico II, via Mezzocannone, 16, 80134 Napoli, Italy; Institute of Biostructures and Bioimaging, National Research Council, IBB-CNR, via Mezzocannone, 16, 80134 Napoli, Italy. Electronic address: [email protected] , (Italy)
  • 8 CIRPeB, University of Naples Federico II, via Mezzocannone, 16, 80134 Napoli, Italy; Institute of Biostructures and Bioimaging, National Research Council, IBB-CNR, via Mezzocannone, 16, 80134 Napoli, Italy; Dept. of Pharmacy, University of Naples Federico II, via Mezzocannone, 16, 80134 Napoli, Italy. Electronic address: [email protected] , (Italy)
Type
Published Article
Journal
Bioorganic & medicinal chemistry
Publication Date
Dec 15, 2017
Volume
25
Issue
24
Pages
6589–6596
Identifiers
DOI: 10.1016/j.bmc.2017.10.036
PMID: 29113739
Source
Medline
Keywords
Language
English
License
Unknown

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. Copyright © 2017 Elsevier Ltd. All rights reserved.

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