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.
Keywords:
cancer; lactam bridge; peptides; phosphatases.
© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Antineoplastic Agents / chemical synthesis
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology*
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Cell Proliferation / drug effects
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Chymotrypsin / chemistry
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Drug Design
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Drug Stability
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Enzyme Activators / chemical synthesis
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Enzyme Activators / chemistry
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Enzyme Activators / pharmacology*
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HeLa Cells
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Humans
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Lactams / chemical synthesis
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Lactams / chemistry
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Lactams / pharmacology*
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Molecular Structure
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Peptides, Cyclic / chemical synthesis
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Peptides, Cyclic / chemistry
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Peptides, Cyclic / pharmacology*
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Proteolysis
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Receptor-Like Protein Tyrosine Phosphatases, Class 3 / metabolism
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Trypsin / chemistry
Substances
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Antineoplastic Agents
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Enzyme Activators
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Lactams
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Peptides, Cyclic
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PTPRJ protein, human
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Receptor-Like Protein Tyrosine Phosphatases, Class 3
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Chymotrypsin
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Trypsin