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Design, Synthesis, Biological Activity and Structural Analysis of lactam-constrained PTPRJ agonist peptides.

Research paper by Marina M Sala, Antonia A Spensiero, Maria Carmina MC Scala, Giacomo G Pepe, Anna A Bilotta, Francesco F Paduano, Sabrina S D'Agostino, Delia D Lanzillotta, Alessia A Bertamino, Ettore E Novellino, Francesco F Trapasso, Isabel Maria IM Gomez-Monterrey, Pietro P Campiglia

Indexed on: 12 Jun '18Published on: 12 Jun '18Published in: 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. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.