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Updated: Jan 27, 2026

Structure and Coordination Determination of Peptide-metal Complexes Using 1D and 2D 1H NMR
Published on: December 16, 2013
QSAR-by-NMR: quantitative insights into structural determinants for binding affinity by analysis of 1H/15N chemical
Hans Matter1, Manfred Schudok, Bettina Elshorst
1Aventis Pharma Deutschland GmbH, DI&A Chemistry, Building G 878, D-65926 Frankfurt am Main, Germany. hans.matter@aventis.com
Abstract:
A novel strategy is applied to obtain quantitative insights on factors influencing biological affinity in protein-ligand complexes. This approach is based on the detection of ligand binding by (15)N and (1)H amide chemical shift differences in two-dimensional (15)N-heteronuclear single-quantum correlation spectra. Essential structural features linked to affinity can be extracted using statistical analysis of (15)N and (1)H amide chemical shift differences in congeneric series relative to uncomplexed protein spectra, as demonstrated for 20 MMP-3 inhibitors in complex with human matrix metalloproteinase stromelysin (MMP-3). The statistical analysis using PLS led to a significant model, while its chemical interpretation, highlighting the importance of particular residues for affinity, are in agreement to an X-ray structure of one key compound in the homologue MMP-8 binding site.
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