Simplified Synthesis and Stability Assessment of Aflatoxin B1-Lysine and Aflatoxin G1-Lysine.

Justin B Renaud,Jacob P Walsh,Mark W Sumarah

doi:10.3390/toxins14010056

Justin B Renaud, Jacob P Walsh + Show 1 more

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https://doi.org/10.3390/toxins14010056

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Journal: Toxins	Publication Date: Jan 14, 2022
Citations: 6	License type: CC BY 4.0

Affiliation: Agriculture and Agri-Food Canada, Western University

Abstract

Aflatoxins B1 (AFB1) and G1 (AFG1) are carcinogenic mycotoxins that contaminate crops such as maize and groundnuts worldwide. The broadly accepted method to assess chronic human aflatoxin exposure is by quantifying the amount of aflatoxin adducted to human serum albumin. This has been reported using ELISA, HPLC, or LC-MS/MS to measure the amount of AFB1-lysine released after proteolysis of serum albumin. LC-MS/MS is the most accurate method but requires both isotopically labelled and unlabelled AFB1-lysine standards, which are not commercially available. In this work, we report a simplified synthetic route to produce unlabelled, deuterated and 13C6 15N2 labelled aflatoxin B1-lysine and for the first-time aflatoxin G1-lysine. Additionally, we report on the stability of these compounds during storage. This simplified synthetic approach will make the production of these important standards more feasible for laboratories performing aflatoxin exposure studies.

Highlights

B1 -Lysine and Aflatoxin G1 -Lysine.Aflatoxins are the most important mycotoxins from a human health perspective, especially in developing countries
We report on the stability of these compounds during storage. This simplified synthetic approach will make the production of these important standards more feasible for laboratories performing aflatoxin exposure studies
Latin-American, and sub-Saharan Africa are being exposed to aflatoxin B1 (AFB1 )

Summary

Introduction

B1 -Lysine and Aflatoxin G1 -Lysine.Aflatoxins are the most important mycotoxins from a human health perspective, especially in developing countries. AFB1 is highly mutagenic, arising from epoxidation of the 8,9 vinyl double bond by human liver P450 enzymes (CYP3A4, CYP1A2, and CYP3A5 in some individuals) [4]. AFB1 8,9 exo-epoxide is considered to be one of the most carcinogenic compounds known [5]. It efficiently chelates between DNA base pairs to react with guanine residues leading to base pair mutations [6]. The carcinogen AFB1 -8,9 exo epoxide hydrolyzes rapidly under aqueous conditions to AFB1 -dihydrodiol which is in equilibrium with AFB1 -dialdehyde [9] (Scheme 1). AFB1 -dialdehyde is highly reactive towards amines [10] and forms covalent adducts with lysine residues within human serum albumin [11,12,13]

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