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Published on: August 4, 2023
Design, Synthesis, Biological Activity, and Structural Analysis of Lactam-Constrained PTPRJ Agonist Peptides
Marina Sala1, Antonia Spensiero1, Maria Carmina Scala1
1Department of Pharmacy, University of Salerno, 84084, Fisciano (SA), Italy.
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 recently identified a disulfide-bridged nonapeptide, named PTPRJ-19 (H-[Cys-His-His-Asn-Leu-Thr-His-Ala-Cys]-OH), which activates PTPRJ, thereby causing cell growth inhibition and apoptosis of both cancer and endothelial cells. With the aim of replacing the disulfide bridge by a chemically more stable moiety, we have synthesized and tested a series of lactam analogues of PTPRJ-19. This replacement led to analogues with higher activity and greater stability than the parent peptide.
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