Site-selective modification of proteins using cucurbit[7]uril as supramolecular protection for: N -terminal aromatic amino acids

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DOI

  • Anton A.A. Smith, Stanford University
  • ,
  • Caitlin L. Maikawa, Stanford University
  • ,
  • Gillie A. Roth, Stanford University
  • ,
  • Eric A. Appel, Stanford University
  • ,
  • Eric A. Appel, Stanford University

Cucurbit[7,8]urils are known to form inclusion complexes with aromatic amino acids, hosting the hydrohobic side chains within the cavity and adjacent cations within the portal of the macrocyclic host. Here we show that cucurbit[7]uril binding with N-terminal phenylalanine significantly reduces the nucleophilicity of the amine, likely due to an increase in stability of the ammonium ion, rendering it unreactive at neutral pH. Using insulin as a model protein, we show that this supramolecular protection strategy can drive selectivity of N-terminal amine conjugation away from the preferred B chain N-terminal phenylalanine towards the A chain N-terminal glycine. Cucurbit[7]uril can therefore be used as a supramolecular protecting group for site-selective protein modification. This journal is

Original languageEnglish
JournalOrganic and Biomolecular Chemistry
Volume18
Issue23
Pages (from-to)4371-4375
Number of pages5
ISSN1477-0520
DOIs
Publication statusPublished - Jun 2020

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