Supramolecular Approach to Electron Paramagnetic Resonance Distance Measurement of Spin-Labeled Proteins

Zhimin Yang, Richard A. Stein, Thacien Ngendahimana, Maren Pink, Suchada Rajca, Gunnar Jeschke, Sandra S. Eaton, Gareth R. Eaton, Hassane S. McHaourab, Andrzej Rajca

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


We demonstrate a host-guest molecular recognition approach to advance double electron-electron resonance (DEER) distance measurements of spin-labeled proteins. We synthesized an iodoacetamide derivative of 2,6-diazaadamantane nitroxide (DZD) spin label that could be doubly incorporated into T4 Lysozyme (T4L) by site-directed spin labeling with efficiency up to 50% per cysteine. The rigidity of the fused ring structure and absence of mobile methyl groups increase the spin echo dephasing time (Tm) at temperatures above 80 K. This enables DEER measurements of distances >4 nm in DZD-labeled T4L in glycerol/water at temperatures up to 150 K with increased sensitivity compared to that of a common spin label such as MTSL. Addition of β-cyclodextrin reduces the rotational correlation time of the label, slightly increases Tm, and most importantly, narrows (and slightly lengthens) the interspin distance distributions. The distance distributions are in good agreement with simulated distance distributions obtained by rotamer libraries. These results provide a foundation for developing supramolecular recognition to facilitate long-distance DEER measurements at near physiological temperatures.

Original languageEnglish (US)
Pages (from-to)3291-3299
Number of pages9
JournalJournal of Physical Chemistry B
Issue number16
StatePublished - Apr 23 2020

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Surfaces, Coatings and Films
  • Materials Chemistry


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