title: Thrombospondin-1 Mimetic Agonist Peptides Induce Selective Death in Tumor Cells: Design, Synthesis, and Structure-Activity Relationship Studies.
abstract: Thrombospondin-1 (TSP-1) is a glycoprotein considered as a key actor within the tumor microenvironment. Its binding to CD47, a cell surface receptor, triggers programmed cell death. Previous studies allowed the identification of 4N1K decapeptide derived from the TSP-1/CD47 binding epitope. Here, we demonstrate that this peptide is able to induce selective apoptosis of various cancer cell lines while sparing normal cells. A structure-activity relationship study led to the design of the first serum stable TSP-1 mimetic agonist peptide able to trigger selective programmed cell death (PCD) of at least lung, breast, and colorectal cancer cells. Altogether, these results will be of valuable interest for further investigation in the design of potent CD47 agonist peptides, opening new perspectives for the development of original anticancer therapies.
authors.affiliation: Sorbonne Universités, UPMC Université Paris 06, Ecole Normale Supérieure, CNRS, Laboratoire des Biomolécules, 75005 Paris, France.|Département de Chimie, Ecole Normale Supérieure, PSL Research University, UPMC Université Paris 06, CNRS, Laboratoire des Biomolécules, 75005 Paris, France.|UPMC Université Paris 06, Laboratoire des BioMolécules, Site GSK, 25-27 Avenue du Québec, 91140 Les Ulis, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Denèfle
authors.affiliation: Sorbonne Universités, UPMC Université Paris 06, Ecole Normale Supérieure, CNRS, Laboratoire des Biomolécules, 75005 Paris, France.|Département de Chimie, Ecole Normale Supérieure, PSL Research University, UPMC Université Paris 06, CNRS, Laboratoire des Biomolécules, 75005 Paris, France.
authors.forename: Héloise
authors.initials: H
authors.lastname: Boullet
authors.affiliation: Cell Death and Drug Resistance in Lymphoproliferative Disorders Team, Centre de Recherche des Cordeliers, INSERM UMRS, 1138, Paris, France.|Sorbonne Universités, UPMC Université Paris 06, UMRS 1138, Paris, France.|Université Paris Descartes, Sorbonne Paris Cité, UMRS 1138, Paris, France.
authors.forename: Linda
authors.initials: L
authors.lastname: Herbi
authors.affiliation: Sorbonne Universités, UPMC Université Paris 06, Ecole Normale Supérieure, CNRS, Laboratoire des Biomolécules, 75005 Paris, France.|Département de Chimie, Ecole Normale Supérieure, PSL Research University, UPMC Université Paris 06, CNRS, Laboratoire des Biomolécules, 75005 Paris, France.|UPMC Université Paris 06, Laboratoire des BioMolécules, Site GSK, 25-27 Avenue du Québec, 91140 Les Ulis, France.
authors.forename: Clara
authors.initials: C
authors.lastname: Newton
authors.affiliation: Cell Death and Drug Resistance in Lymphoproliferative Disorders Team, Centre de Recherche des Cordeliers, INSERM UMRS, 1138, Paris, France.|Sorbonne Universités, UPMC Université Paris 06, UMRS 1138, Paris, France.|Université Paris Descartes, Sorbonne Paris Cité, UMRS 1138, Paris, France.
authors.forename: Ana-Carolina
authors.initials: AC
authors.lastname: Martinez-Torres
authors.affiliation: Sorbonne Universités, UPMC Université Paris 06, Ecole Normale Supérieure, CNRS, Laboratoire des Biomolécules, 75005 Paris, France.|Département de Chimie, Ecole Normale Supérieure, PSL Research University, UPMC Université Paris 06, CNRS, Laboratoire des Biomolécules, 75005 Paris, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Guez
authors.affiliation: Sorbonne Universités, UPMC Université Paris 06, Ecole Normale Supérieure, CNRS, Laboratoire des Biomolécules, 75005 Paris, France.|Département de Chimie, Ecole Normale Supérieure, PSL Research University, UPMC Université Paris 06, CNRS, Laboratoire des Biomolécules, 75005 Paris, France.|Cell Death and Drug Resistance in Lymphoproliferative Disorders Team, Centre de Recherche des Cordeliers, INSERM UMRS, 1138, Paris, France.|Sorbonne Universités, UPMC Université Paris 06, UMRS 1138, Paris, France.|Université Paris Descartes, Sorbonne Paris Cité, UMRS 1138, Paris, France.
authors.forename: Elodie
authors.initials: E
authors.lastname: Pramil
authors.affiliation: Cell Death and Drug Resistance in Lymphoproliferative Disorders Team, Centre de Recherche des Cordeliers, INSERM UMRS, 1138, Paris, France.|Sorbonne Universités, UPMC Université Paris 06, UMRS 1138, Paris, France.|Université Paris Descartes, Sorbonne Paris Cité, UMRS 1138, Paris, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Quiney
authors.affiliation: Sorbonne Universités, UPMC Université Paris 06, Ecole Normale Supérieure, CNRS, Laboratoire des Biomolécules, 75005 Paris, France.|Département de Chimie, Ecole Normale Supérieure, PSL Research University, UPMC Université Paris 06, CNRS, Laboratoire des Biomolécules, 75005 Paris, France.|UPMC Université Paris 06, Laboratoire des BioMolécules, Site GSK, 25-27 Avenue du Québec, 91140 Les Ulis, France.
authors.forename: Marilyne
authors.initials: M
authors.lastname: Pourcelot
authors.affiliation: Sorbonne Universités, UPMC Université Paris 06, Ecole Normale Supérieure, CNRS, Laboratoire des Biomolécules, 75005 Paris, France.|Département de Chimie, Ecole Normale Supérieure, PSL Research University, UPMC Université Paris 06, CNRS, Laboratoire des Biomolécules, 75005 Paris, France.|UPMC Université Paris 06, Laboratoire des BioMolécules, Site GSK, 25-27 Avenue du Québec, 91140 Les Ulis, France.
authors.forename: Mikail D
authors.initials: MD
authors.lastname: Levasseur
authors.affiliation: Sorbonne Universités, UPMC Université Paris 06, Ecole Normale Supérieure, CNRS, Laboratoire des Biomolécules, 75005 Paris, France.|Département de Chimie, Ecole Normale Supérieure, PSL Research University, UPMC Université Paris 06, CNRS, Laboratoire des Biomolécules, 75005 Paris, France.|UPMC Université Paris 06, Laboratoire des BioMolécules, Site GSK, 25-27 Avenue du Québec, 91140 Les Ulis, France.
authors.forename: Eva
authors.initials: E
authors.lastname: Lardé
authors.affiliation: Sorbonne Universités, UPMC Université Paris 06, Ecole Normale Supérieure, CNRS, Laboratoire des Biomolécules, 75005 Paris, France.|Département de Chimie, Ecole Normale Supérieure, PSL Research University, UPMC Université Paris 06, CNRS, Laboratoire des Biomolécules, 75005 Paris, France.
authors.forename: Roba
authors.initials: R
authors.lastname: Moumné
authors.affiliation: NanoTemper Technologies GmbH, Floessergasse 4, 81369 Munich, Germany.
authors.forename: François-Xavier
authors.initials: FX
authors.lastname: Ogi
authors.affiliation: GSK, 25 Avenue du Québec, 91140 Les Ulis, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Grondin
authors.affiliation: Cell Death and Drug Resistance in Lymphoproliferative Disorders Team, Centre de Recherche des Cordeliers, INSERM UMRS, 1138, Paris, France.|Sorbonne Universités, UPMC Université Paris 06, UMRS 1138, Paris, France.|AP-HP, GH Pitié-Salpêtrière, Service d'Hématologie Biologique, 75013 Paris, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Merle-Beral
authors.affiliation: Sorbonne Universités, UPMC Université Paris 06, Ecole Normale Supérieure, CNRS, Laboratoire des Biomolécules, 75005 Paris, France.|Département de Chimie, Ecole Normale Supérieure, PSL Research University, UPMC Université Paris 06, CNRS, Laboratoire des Biomolécules, 75005 Paris, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Lequin
authors.affiliation: Cell Death and Drug Resistance in Lymphoproliferative Disorders Team, Centre de Recherche des Cordeliers, INSERM UMRS, 1138, Paris, France.|Sorbonne Universités, UPMC Université Paris 06, UMRS 1138, Paris, France.|Université Paris Descartes, Sorbonne Paris Cité, UMRS 1138, Paris, France.
authors.forename: Santos A
authors.initials: SA
authors.lastname: Susin
authors.affiliation: Sorbonne Universités, UPMC Université Paris 06, Ecole Normale Supérieure, CNRS, Laboratoire des Biomolécules, 75005 Paris, France.|Département de Chimie, Ecole Normale Supérieure, PSL Research University, UPMC Université Paris 06, CNRS, Laboratoire des Biomolécules, 75005 Paris, France.|UPMC Université Paris 06, Laboratoire des BioMolécules, Site GSK, 25-27 Avenue du Québec, 91140 Les Ulis, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Karoyan
mesh_terms: D000595:Amino Acid Sequence; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D006801:Humans; D008958:Models, Molecular; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D019700:Thrombospondin 1 / Q000819:agonists* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D010455:Peptides; D019700:Thrombospondin 1