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New Peptides Structurally Related to VEGF-A165 Exon-7 and -8 Encoded Domains Antagonize Its Binding to NRP-1 and VEGF-R1

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Abstract

We report in the present study the design, synthesis and preliminary biological evaluations of linear, short-sized, and polymeric peptides asVEGF-A165 binding to NRP-1 and/or VEGF-R1 antagonists. These newly-synthesized peptides are structurally related to the VEGF-A165 domains encoded by exon-7 and -8. Thus, the key role of exon-7 encoded cysteine residues, and the relevance of the C-terminal peptide chemical function (amide or acid) were demonstrated. Indeed, COOH-terminal peptides showed a good selectivity for NRP-1, while CONH2-terminal peptides did not. Taking advantage of these results, we designed original VEGF-A165 binding to NRP-1 and VEGF-R1 polymeric peptide antagonists, which showed potent HUVEC anti-proliferative activity. Finally, this work paved the way for the design of future therapeutics targeting the VEGF-A165 angiogenic signaling pathway.

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Acknowledgments

This study was supported by Grant from the “Institute National du Cancer” (INCa “ANGIOMED”, 2007–2010 Grant). LB was supported by a “Leonardo da Vinci” Grant (Unipharma graduate, Noopolis Fundation, Rome, Italy) for her research. The authors are thankful to Drs. Rachid Benhida and Nadine Martinet for the critical reviewing of this article.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. INSERM U648, Laboratory of Molecular and Cellular Pharmacochemistry, Paris Descartes, University-Sorbonne Paris Cité, UFR Biomédicale des Saints Pères, 45 rue des Saints Pères, 75270, Paris Cedex 06, France

    Wang-Qing Liu, Lucia Borriello, Barbara Allain, Christiane Garbay, Françoise Raynaud & Luc Demange

  2. Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques (LCBPT), UMR 8601 CNRS, University-Paris Descartes, Sorbonne Paris Cité, UFR Biomédicale des Saints Pères, 45 rue des Saints Pères, 75270, Paris Cedex 06, France

    Lucia Borriello, Serena Pavoni, Christiane Garbay, Françoise Raynaud & Luc Demange

  3. ESG, 59 Rue Nationale, 75013, Paris, France

    Nicolas Lopez

  4. INSERM UMR 1163, Laboratory of Cellular and Molecular Basis of Normal Hematopoiesis and Hematological Disorders, 24 boulevard Montparnasse, 75015, Paris, France

    Olivier Hermine & Yves Lepelletier

  5. Paris Descartes, University-Sorbonne Paris Cité, Imagine Institute, 24 boulevard Montparnasse, 75015, Paris, France

    Olivier Hermine & Yves Lepelletier

  6. CNRS ERL 8254, 24 boulevard Montparnasse, 75015, Paris, France

    Olivier Hermine & Yves Lepelletier

  7. Institut de Chimie de Nice (ICN), UMR 7272 CNRS, Université de Nice Sophia-Antipolis, Parc Valrose, 06108, Nice, France

    Luc Demange

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  1. Wang-Qing Liu
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  2. Lucia Borriello
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  3. Barbara Allain
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  4. Serena Pavoni
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  5. Nicolas Lopez
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  7. Christiane Garbay
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  8. Françoise Raynaud
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  9. Yves Lepelletier
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  10. Luc Demange
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Correspondence to Yves Lepelletier or Luc Demange.

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Liu, WQ., Borriello, L., Allain, B. et al. New Peptides Structurally Related to VEGF-A165 Exon-7 and -8 Encoded Domains Antagonize Its Binding to NRP-1 and VEGF-R1. Int J Pept Res Ther 21, 117–124 (2015). https://doi.org/10.1007/s10989-014-9436-6

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