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Modeling Ligands into Maps Derived from Electron Cryomicroscopy
Published on: July 19, 2024
Structural features and hydrogen-bond properties of galanthamine and codeine: an experimental and theoretical study
Alexandre P Atkinson1, Evelyne Baguet, Nicolas Galland
1Laboratoire CEISAM, UMR 6230 CNRS, Faculté des Sciences et des Techniques de Nantes, 2, rue de la Houssinière, BP 92208, 44322 Nantes Cedex 3, France.
Chemistry (Weinheim an Der Bergstrasse, Germany)
|September 3, 2011
Summary
Galanthamine and codeine, nicotinic acetylcholine receptor (nAChR) modulators, show distinct hydrogen bonding. Galanthamine exhibits stronger intramolecular hydrogen bonds and higher hydrogen-bond accepting strength than codeine.
Area of Science:
- Medicinal Chemistry
- Structural Biology
- Computational Chemistry
Background:
- Galanthamine and codeine are allosteric potentiators of nicotinic acetylcholine receptors (nAChRs).
- Understanding their structural features and interactions is crucial for drug design.
Purpose of the Study:
- To investigate the structural differences between galanthamine and codeine in solution.
- To elucidate the nature and strength of hydrogen bonding and other interactions in these ligands.
- To compare their interactions with acetylcholine esterase (AChE) and acetylcholine binding protein (AChBP).
Main Methods:
- Fourier Transform Infrared (FTIR) spectroscopy to study hydrogen bonding.
- Nuclear Magnetic Resonance (NMR) spectroscopy, including NOE measurements, for structural analysis.
- Quantum chemical calculations (e.g., NBO analysis, MESP) for theoretical insights.
Main Results:
- Galanthamine possesses a stronger intramolecular OH···O hydrogen bond compared to codeine.
- NMR data indicate CH···O hydrogen bonds and a favored trans orientation of the methoxy group in polar solvents.
- Galanthamine exhibits significantly higher hydrogen-bond accepting strength than codeine, attributed to its hydroxyl and amino groups.
- Differences observed in interactions with AChE, but similar interactions with AChBP.
Conclusions:
- Structural and electronic differences, particularly in hydrogen bonding, distinguish galanthamine and codeine.
- These differences influence their interactions with biological targets like AChE.
- The study provides a detailed molecular understanding of these nAChR modulators.
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