Optimized co-solute paramagnetic relaxation enhancement for the rapid NMR analysis of a highly fibrillogenic peptide

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  • Nur Alia Oktaviani, University of Groningen, Netherlands
  • Michael W Risør
  • ,
  • Young-Ho Lee, Osaka University, Japan
  • Rik P Megens, University of Groningen, Netherlands
  • Djurre H de Jong, University of Groningen, Netherlands
  • Renee Otten, University of Groningen, Netherlands
  • Ruud M Scheek, University of Groningen, Netherlands
  • Jan J Enghild
  • Niels Christian Nielsen
  • Takahisa Ikegami, Osaka University, Japan
  • Frans A A Mulder

Co-solute paramagnetic relaxation enhancement (PRE) is an attractive way to speed up data acquisition in NMR spectroscopy by shortening the T 1 relaxation time of the nucleus of interest and thus the necessary recycle delay. Here, we present the rationale to utilize high-spin iron(III) as the optimal transition metal for this purpose and characterize the properties of its neutral chelate form Fe(DO3A) as a suitable PRE agent. Fe(DO3A) effectively reduces the T 1 values across the entire sequence of the intrinsically disordered protein α-synuclein with negligible impact on line width. The agent is better suited than currently used alternatives, shows no specific interaction with the polypeptide chain and, due to its high relaxivity, is effective at low concentrations and in 'proton-less' NMR experiments. By using Fe(DO3A) we were able to complete the backbone resonance assignment of a highly fibrillogenic peptide from α1-antitrypsin by acquiring the necessary suite of multidimensional NMR datasets in 3 h.

Original languageEnglish
JournalJournal of Biomolecular N M R
Volume62
Issue2
Pages (from-to)129-142
Number of pages14
ISSN0925-2738
DOIs
Publication statusPublished - Jun 2015

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