Thrombospondin-1 Mimetic Agonist Peptides Induce Selective Death in Tumor Cells: Design, Synthesis, and Structure-Activity Relationship Studies.
J Med Chem
; 59(18): 8412-21, 2016 09 22.
Article
em En
| MEDLINE
| ID: mdl-27526615
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Peptídeos
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Trombospondina 1
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Antineoplásicos
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article