Synthesis and Biological Evaluation of an N6-Diethylphospholysyl-Containing Peptide-A Model Compound with a Covalently Attached Metabolite of an Organophosphate Pesticide

Release of Covalently Bound Metabolites of Organophosphate Pesticides from Synthetic Dialkylphosphoseryl Peptides by Supercritical Fluid Extraction

“…Since the germ layer is the physiologically most active part of cereal grains, the author assumed that this is where much of the metabolism and formation of bound residues occur. Thus, covalent binding involving phosphorylation of proteins with pesticides in the germ layer would affect the biologically most important proteins (Paquet et al, 1994). It would be, therefore, of importance to be able to detect the presence of covalently attached metabolites of pesticides in grains.…”

Use of NMR techniques for toxic organophosphorus compound profiling

“…Paquet and Khan [107] investigated the efficiency of supercritical fluid extraction (SFE) in plant component analysis in order to find a way to extract metabolites of OP pesticides covalently bound to serine residues of proteins in plants or grains. The phosphorylation of proteins with pesticides can reduce the nutritive value of cereal grain proteins [108]. They used model dialkyl phosphoserine peptides bound to solid support resin.…”

Nutritional and Toxicological Assessment of an N6-Diethylphospholysyl Peptide: A Synthetic Compound Resembling the Covalently Bound Metabolite of an Organophosphate Pesticide to Protein-Bound Lysine

“…For example, phosphorylation of the N 6 -amino group of lysine, which is a stronger nucleophile than the hydroxy group of serine, has not been considered. An organophosphate pesticide, possessing essentially the structure of an active ester (Paquet et al, 1994), could react with the N 6 -terminal amino group of lysine at a rate higher than that with the hydroxy group of serine at a nonspecific site. Matthews (1988) showed that major metabolic process of 14 C-labeled melathion and chlorpyrifos-methyl in stored wheat is formation of unextractable residues in the germ layer.…”

“…A model peptide containing N 6 -diethylphospholysine on an internal position, Ac-Ala-Lys(PO 3 Et 2 )-Val-OEt, and two nonphosphorylated counterparts, Ac-Ala-Lys-Val-OEt and Ac-Tyr-Lys-Val-OEt, were synthesized in high yields and fully characterized by physiochemical constants, HPLC, NMR, and mass spectra (Paquet et al, 1994). A preliminary feeding study suggested that lysine was completely unavailable to weanling rats from its N 6 -diethylphospho derivative bound in a synthetic model peptide, Ac-Ala-Lys(PO 3 Et 2 )-Val-OEt, whereas values for bioavailability of lysine in the two nonphosphorylated peptides, Ac-Ala-Lys-Val-OEt and Ac-Tyr-Lys-Val-OEt, were 79 and 95%, respectively (Paquet et al, 1994).…”

“…The feeding study of Paquet et al (1994) was of short duration (1 week), and the phosphorylated model peptide was tested at a low dietary level (0.3%). Further studies including longer duration and higher dietary * Author to whom correspondence should be addressed.…”