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

Published

Journal Article

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.

Full Text

Cited Authors

  • Oktaviani, NA; Risør, MW; Lee, Y-H; Megens, RP; de Jong, DH; Otten, R; Scheek, RM; Enghild, JJ; Nielsen, NC; Ikegami, T; Mulder, FAA

Published Date

  • June 2015

Published In

Volume / Issue

  • 62 / 2

Start / End Page

  • 129 - 142

PubMed ID

  • 25820763

Pubmed Central ID

  • 25820763

Electronic International Standard Serial Number (EISSN)

  • 1573-5001

International Standard Serial Number (ISSN)

  • 0925-2738

Digital Object Identifier (DOI)

  • 10.1007/s10858-015-9925-8

Language

  • eng