Revealing Organophosphorus and Carbamate Interactions with Albumin Using 1H NOE Pumping NMR Technique

TL;DR

This study uses NMR to explore how toxic compounds bind to albumin, revealing new insights into their interactions at the atomic level.

Contribution

The study introduces the use of 1H NOE pumping NMR for ligand competition studies with BSA using a single sample.

Findings

Amiton and aminostigmine showed stronger binding to BSA compared to dimethoate and carbofuran.

The 1H NOE pumping technique revealed that OP and CM compounds bind to a common epitope site on BSA.

This is the first NMR-based comparative study of OP and CM compounds with BSA.

Abstract

In this work, the
capability of the 1H nuclear
Overhauser
effect (NOE) pumping NMR technique was applied to elucidate the atomic-level
binding interaction between the bovine serum albumin (BSA) and four
toxic compounds: amiton, dimethoate, carbofuran, and aminostigmine.
With the aid of 1H NOE pumping experiments, we were able
to highlight ligand binding epitopes for the studied compounds and
provide prefatory data for the ligand affinity with BSA via dissociation
constant values (K
D). In addition, we
demonstrate that the 1H NOE pumping technique is suitable
for the ligand competition studies solely using one NMR sample and
that the technique is a simple and straightforward method capable
of revealing important parameters that are used typically to define
ligand–albumin interaction at the atomic level. We believe
the novel precursory results herein provide important and experimentally
driven data for the BSA interaction, especially for carbamate-based
molecules, where the existing literature is fairly limited. Based
on the preliminary experimental results, amiton and aminostigmine
showed stronger binding to BSA based on NOE pumping data compared
with dimethoate and carbofuran, although the obtained K
D values were observed within a similar range. Our results
present the first comparable study between the organophosphorus (OP)
and the carbamate (CM) toxic compounds with BSA via NMR spectroscopy
only. Furthermore, the efficacy of the 1H NOE pumping technique
provided evidence that the organophosphorus and carbamate compounds
bind to a common epitope site on BSA.

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