Abstract
The synthesis of a sulfonamide-based transition-state (TS) analogue of enzymatic phosphohistidine dephosphorylation as an amino acid building block is presented, together with the proof-of-concept of its incorporation into peptides. Key features include final global acidolytic protective group removal as well as full compatibility with standard Fmoc solid-phase peptide synthesis (SPPS). The peptides are designed as inhibitors of phosphohistidine phosphatase and as a pull-down probe for identification of phosphohistidine phosphatases, respectively.
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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Amino Acids / chemistry
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Drug Design
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / metabolism
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Fluorenes / chemistry
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Humans
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Magnetic Resonance Spectroscopy
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Molecular Mimicry
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Molecular Sequence Data
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Molecular Structure
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Peptides / chemical synthesis*
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Peptides / metabolism
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Phosphoric Monoester Hydrolases / chemistry*
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Phosphoric Monoester Hydrolases / metabolism
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Solid-Phase Synthesis Techniques
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Sulfonamides / chemical synthesis*
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Sulfonamides / metabolism
Substances
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Amino Acids
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Enzyme Inhibitors
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Fluorenes
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N(alpha)-fluorenylmethyloxycarbonylamino acids
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Peptides
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Sulfonamides
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PHPT1 protein, human
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Phosphoric Monoester Hydrolases