Permethylation is a common derivatization method for MS-based glycomic analyses. Permethylation enhances glycan ionization efficiency in positive MS analysis and improves glycan structural stability. Recent biological glycomic studies have added to the growing body of knowledge and suggest the need for complete structural analysis of glycans. However, reverse phase LC analysis of permethylated glycans usually results in poor isomeric separation. To achieve isomeric separation of permethylated glycans, a porous graphitic carbon (PGC) column was used. PGC columns are well known for their isomeric separation capability for hydrophilic analyses. In this study, we have optimized temperature conditions to overcome the issues encountered while separating permethylated glycans on a PGC column and found that the highest temperature examined, 75°C, was optimal. Additionally, we utilized tandem MS to elucidate detailed structural information for the isomers separated. Glycan standards were also utilized to facilitate structural identifications through MS/MS spectra and retention time comparison. The result is an efficient and sensitive method capable of the isomeric separation of permethylated glycans. This method was successfully applied for the isomeric characterization of N-glycans released from the breast cancer cell lines MDA-MB-231 and MDA-MB-231BR (brain seeking). A total of 127 unique glycan structures were identified with 39 isobaric structures, represented as 106 isomers, with 21 non-isomeric glycans. Thirty seven structures exhibited significant differences in isomeric distribution (P < 0.05). Additionally, alterations in the distribution of isomeric sialylated glycans, structures known to be involved in cell attachment to the blood-brain barrier during brain metastasis, were observed.

“Novichoks” is the name given to the controversial chemical weapons supposedly developed in the former Soviet Union between the 1970s and the 1990s. Designed to be undetectable and untreatable, these chemicals became the most toxic of the nerve agents, being very attractive for both terrorist and chemical warfare purposes. However, very little information is available in the literature, and the Russian government did not acknowledge their development. The intent of this review is to provide the IJMS readers with a general overview on what is known about novichoks today. We briefly tell the story of the secret development of these agents, and discuss their synthesis, toxicity, physical-chemical properties, and possible ways of treatment and neutralization. In addition, we also wish to call the attention of the scientific community to the great risks still represented by nerve agents worldwide, and the need to keep constant investments in the development of antidotes and ways to protect against such deadly compounds.

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Casualties caused by organophosphorus pesticides are a burden for health systems in developing and poor countries. Such compounds are potent acetylcholinesterase irreversible inhibitors, and share the toxic profile with nerve agents. Pyridinium oximes are the only clinically available antidotes against poisoning by these substances, but their poor penetration into the blood-brain barrier hampers the efficient enzyme reactivation at the central nervous system. In searching for structural factors that may be explored in future SAR studies, we evaluated neutral aryloximes as reactivators for paraoxon-inhibited Electrophorus eel acetylcholinesterase. Our findings may result into lead compounds, useful for development of more active compounds for emergencies and supportive care.

Straightforward, microscale, Ellman's cholinesterase test procedures are presented, useful for screening of novel compounds aiming at neurodegenerative diseases and antidotes towards nerve agents and pesticides. Herein, we detail the different procedure features and set forth guidelines on experimental choices researchers may make. The detailed procedure lowers the costs for Ellman´s test, what is highly desirable for low-budget groups in science-lagging and developing countries.