The Rigid Nitroxide Side Chain
  • Joseph C. McNulty
  • Glenn L. Millhauser
Part of the Biological Magnetic Resonance book series (BIMR, volume 19)


TOAC (2,2,6,6-tetramethylpiperidine-1-oxyl-4-amino-4-carboxylic acid) is an unnatural amino acid that contains a nitroxide ring rigidly attached at the backbone alpha carbon. Because the conformation of TOAC is highly constrained, distances determined between pairs of TOACs are not compromised by uncertainties in nitroxide side chain orientations. ESR detected interactions between TOACs have revealed accurate distances out to beyond 10 Å and, correspondingly, exciting new structural insights into the folds of both model and naturally occurring peptides. TOAC’s history is recent, with the first report of its incorporation into a peptide via solid phase synthesis appearing in 1993 (Marchetto et al., 1993). While TOAC does offer significant advantages for biomolecular labeling, its incorporation presents unique challenges in peptide synthesis and design. This chapter will briefly describe synthesis of TOAC-containing peptides, placement within peptide secondary structure, spectroscopy and recent applications.


Electron Spin Resonance Spin Label Dipolar Coupling Hyperfine Line Helical Peptide 
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Copyright information

© Kluwer Academic / Plenum Publishers, New York 2002

Authors and Affiliations

  • Joseph C. McNulty
    • 1
  • Glenn L. Millhauser
    • 1
  1. 1.Department of Chemistry and BiochemistryUniversity of CaliforniaSanta CruzUSA

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