Lecture
Current Progress in Protein-adduct analysis for the verification of poisoning
- at -
- ICM Saal 5
- Type: Lecture
Lecture description
Even though banned by the Chemical Weapons Convention (CWC), certain toxic chemicals were used in the more recent past for poisoning people in warfare scenarios and for (attempted) assassination of individuals. Appropriate bioanalytical methods are thus required not only for toxicological reasons but also for forensic investigations of biological samples like plasma, urine or hair. For this purpose of biomedical verification of exposure laboratories designated by the Organisation for the Prohibition of Chemical Weapons (OPCW) are specialized on the detection of selective biomarkers making the fingerprint of a certain agent visible. Due to their high in vivo stability reaction products of the agents with endogenous proteins represent highly beneficial biomarkers that are targeted by analytical methods. Adducts essential for verification are formed by e.g. alkylating blister agents (according to e.g. annex 1 A4 of the CWC); phosphylating nerve agents (e.g. annex 1 A, 1 B, 2 B1) and organophosphorus (OP) pesticides as well as disulfide-forming leaving groups of V-type nerve agents (annex 1 A3) and some OP pesticides. In addition, adducts may also result from exposure to riot control agents including o-chlorobenzylidene malononitrile (CS) and chloroacetophenone (CN) [1] used as tear gases and malodorous mercaptans [2, 3] and chlorine gas. The use of these chemicals in warfare is also forbidden by the CWC.
This lecture provides an overview on established methods relevant for the verification of exposure to some chemical warfare agents and introduce novel developments and analytical achievements [1-5] helpful to document the violation of international treaties.
Literature:
[1] Sieber PH, Steinritz D, Worek F, John H. Toxic tear gas 2-chloroacetophenone (CN) forms adducts with endogenous plasma thiols in vitro valuable as biomarkers of exposure. Drug Test. Anal. (in press)
[2] Sieber PH, Steinritz D, Worek F, John H. Disulfide-adducts with cysteine residues in human serum albumin prove exposure to malodorous mercaptans in vitro. Anal. Biochem. 2024, 692:115568
[3] Sieber PH, Steinritz D, Worek F, John H. Malodorous mercaptans break disulfide-bridges in human serum albumin and form adducts suitable as biomarkers of exposure in vitro. Drug Test. Anal. 2025, 17:722-734
[4] Schmeißer W, Siegert M, Thiermann H, Rein T, John H. Highly stable peptide adducts from hard keratins as biomarkers to verify local sulfur mustard exposure of hair by high-resolution mass spectrometry. Arch. Toxicol. 2022, 96:2287-2298
[5] Kranawetvogl T, Siegert M, Steinritz D, Thiermann H, John H. The phosphylated butyrylcholinesterase-derived tetrapeptide GlyGluSerAla proves exposure to organophosphorus agents with enantioselectivity. Arch. Toxicol. 2024, 98:791-806
This lecture provides an overview on established methods relevant for the verification of exposure to some chemical warfare agents and introduce novel developments and analytical achievements [1-5] helpful to document the violation of international treaties.
Literature:
[1] Sieber PH, Steinritz D, Worek F, John H. Toxic tear gas 2-chloroacetophenone (CN) forms adducts with endogenous plasma thiols in vitro valuable as biomarkers of exposure. Drug Test. Anal. (in press)
[2] Sieber PH, Steinritz D, Worek F, John H. Disulfide-adducts with cysteine residues in human serum albumin prove exposure to malodorous mercaptans in vitro. Anal. Biochem. 2024, 692:115568
[3] Sieber PH, Steinritz D, Worek F, John H. Malodorous mercaptans break disulfide-bridges in human serum albumin and form adducts suitable as biomarkers of exposure in vitro. Drug Test. Anal. 2025, 17:722-734
[4] Schmeißer W, Siegert M, Thiermann H, Rein T, John H. Highly stable peptide adducts from hard keratins as biomarkers to verify local sulfur mustard exposure of hair by high-resolution mass spectrometry. Arch. Toxicol. 2022, 96:2287-2298
[5] Kranawetvogl T, Siegert M, Steinritz D, Thiermann H, John H. The phosphylated butyrylcholinesterase-derived tetrapeptide GlyGluSerAla proves exposure to organophosphorus agents with enantioselectivity. Arch. Toxicol. 2024, 98:791-806
