Title
Design, Synthesis, Biological Activity and Structural Analysis of lactam‐constrained PTPRJ agonist peptides
Author
Marina Sala, Antonia Spensiero, Maria Carmina Scala, Giacomo Pepe, Anna Bilotta, Francesco Paduano, Sabrina D'Agostino, Delia Lanzillotta, Alessia Bertamino, Ettore Novellino, Francesco Trapasso, Isabel Maria Gomez-Monterrey, Pietro Campiglia
Year
2018
Journal
ChemMedChem
Abstract
PTPRJ is a receptor‐like protein tyrosine phosphatase mainly known for its antiproliferative and tumor‐suppressive functions. PTPRJ dephosphorylates several growth factors and their receptors, negatively regulating cell proliferation and migration. We have recently identified a disulfide bridged nonapeptide, named PTPRJ‐19 (H‐[Cys‐His‐His‐Asn‐Leu‐Thr‐His‐Ala‐Cys]‐OH), which activates PTPRJ causing cell growth inhibition and apoptosis of both cancer and endothelial cells. In the present study, we have synthesized seven analogues of PTPRJ‐19 in which the disulfide bridge was replaced by the side‐chain to side‐chain lactam bridge. This replacement led to active analogues.
Instrument
J-810
Keywords
Circular dichroism, Secondary structure, Aggregation, Chemical stability, Biochemistry