Abstract
beta-Turn peptidomimetics 1 were designed to mimic hot spots of neurotrophin-3 (NT-3) and others. Solid-phase syntheses of these were developed, though limitations were encountered with scale-up. Consequently, an alternative design with 2 was investigated. 1 and 2 favored distorted type I beta-turn conformations in solution. It was found that peptidomimetic 2b has NT-3-like neurotrophic activity in cell survival assays, selectively binds the NT-3 receptor TrkC, and induces the tyrosine phosphorylation of the TrkC receptor.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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3T3 Cells
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Animals
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Cell Survival / drug effects
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Circular Dichroism
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Flow Cytometry
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Mice
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Molecular Mimicry
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Neurotrophin 3 / chemistry*
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Peptides / chemistry*
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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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Phosphorylation
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Protein Structure, Secondary
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Receptor, trkA / metabolism
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Receptor, trkC / metabolism
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Tyrosine / metabolism
Substances
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Neurotrophin 3
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Peptides
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Peptides, Cyclic
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cyclo(lysyl-serinamido-4-carbamoylphenylmethylamino-3-nitrobenzoyl)
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Tyrosine
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Receptor, trkA
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Receptor, trkC