Abstract
Human exposure to the hepatocarcinogenic mycotoxin aflatoxin B1 results in modification of serum albumin lysine ε-amino residues to form lysine-aflatoxin adducts. A perdeuterated reference standard is now required to quantitatively measure this adduct in epidemiologic studies of liver cancer using isotopic dilution mass spectrometry. A convenient method for the preparation of D4-L-lysine-AFB1 using commercially available 5,5,6,6-D4-L-lysine is demonstrated for the first time. The application of two standard α-amino protection methods is also reported that simplifies the production of natural isotopic abundance lysine-AFB1 over the currently used method employing Nα-acetyl-L-lysine. t-Boc-Nα-lysine was used to prepare lysine-AFB1; however, a preferred method for directing reaction of AFB1-dialdehyde to the ε-amino group of 5,5,6,6-D4-L-lysine utilized cupric ions that were spontaneously removed during the reverse phase HPLC purification of D4-lysine-AFB1 using 1% HOAc. This strategy eliminates the need to otherwise synthesize and purify t-Boc-Nα- or N α-acetyl-5,5,6,6-D4-lysine and then TFA or enzymatically deprotect overnight to obtain the target compound.
Original language | English (US) |
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Pages (from-to) | 807-815 |
Number of pages | 9 |
Journal | Journal of Labelled Compounds and Radiopharmaceuticals |
Volume | 47 |
Issue number | 11 |
DOIs | |
State | Published - Oct 15 2004 |
Keywords
- Copper
- D4-lysine
- Isotope dilution mass spectrometry
- Lysine-aflatoxin adduct
- α-amino group protection
ASJC Scopus subject areas
- Analytical Chemistry
- Biochemistry
- Radiology Nuclear Medicine and imaging
- Drug Discovery
- Spectroscopy
- Organic Chemistry