Abstract
We previously demonstrated that ammonium- or guanidinium-phosphate interactions are key to forming noncovalent complexes (NCXs) through salt bridge formation with G-protein coupled receptors (GPCR), which are immersed in the cell membrane's lipids. The present work highlights MALDI ion mobility coupled to orthogonal time-of-flight mass spectrometry (MALDI IM oTOF MS) as a method to determine qualitative and relative quantitative affinity of drugs to form NCXs with targeted GPCRs' epitopes in a model system using, bis-quaternary amine based drugs, α- and β- subunit epitopes of the nicotinic acetylcholine receptor' (nAChR) and phospholipids. Bis-quaternary amines proved to have a strong affinity for all nAChR epitopes and negatively charged phospholipids, even in the presence of the physiological neurotransmitter acetylcholine. Ion mobility baseline separated isobaric phosphatidyl ethanolamine and a matrix cluster, providing an accurate estimate for phospholipid counts. Overall this technique is a powerful method for screening drugs' interactions with targeted lipids and protein respectively containing quaternary amines and guanidinium moieties.
Original language | English (US) |
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Pages (from-to) | 3382-3389 |
Number of pages | 8 |
Journal | Journal of Proteome Research |
Volume | 11 |
Issue number | 6 |
DOIs | |
State | Published - Jun 1 2012 |
Externally published | Yes |
Keywords
- drug-lipid interactions
- Drug-protein interactions
- guanidinium
- MALDI-IM-TOF MS
- noncovalent complexes
- phospholipids
- quaternary amines
ASJC Scopus subject areas
- Biochemistry
- Chemistry(all)
- Medicine(all)