The interaction of n-alkanols with lipid bilayer membranes: a 2H-NMR study.
Temperature; Molecular Conformation; Magnetic Resonance Spectroscopy; *Lipid Bilayers; *Alcohols; *Membrane Lipids; Dimyristoylphosphatidylcholine
The interaction of eight n-alkanols with bilayers of dimyristoylphosphatidylcholine (DMPC) has been studied by deuterium nuclear magnetic resonance (2H-NMR). At comparable temperatures and concentrations of solute in the bilayer, order parameters measured at the 1-methylene segment of the n-alkanols show a maximum for n-dodecanol. For both n-dodecanol and n-tetradecanol, orientational ordering shows a maximum at the C-4 to C-7 methylene segments, with labels at both ends of the n-alkanol exhibiting reduced order. These observations are consistent with earlier findings for n-octanol and n-decanol. Unlike the longer chain n-alkanols, ordering in n-butanol decreases from the hydroxyl group end to the methyl group end of the molecule. Orientational ordering at nine inequivalent sites in DMPC, has also been measured as a function of temperature, for bilayers containing n-butanol, n-octanol, n-dodecanol and n-tetradecanol. At the 3R,S sites on the glycerol backbone, for comparable temperatures and solute concentrations, n-butanol produces a larger disordering than the other n-alkanols. This result probably reflects the greater fraction of time spent by the hydroxyl group of n-butanol in the vicinity of the lipid polar head group compared with the hydroxyl group in longer chain n-alkanols. It was found that n-octanol orders the acyl chains of DMPC, unlike n-butanol which disorders them, and the longer chain n-alkanols which have little effect. Within experimental error, the effect of n-dodecanol on order at all sites in DMPC is the same as n-tetradecanol. The influence of n-alkanols on DMPC ordering at twelve sites has been compared with that of cholesterol which is shown to interact with DMPC bilayers in a distinctly different manner from the n-alkanols.
Westerman P W; Pope J M; Phonphok N; Doane J W; Dubro D W
Biochimica et biophysica acta
1988
1988-03
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/0005-2736(88)90048-x" target="_blank" rel="noreferrer noopener">10.1016/0005-2736(88)90048-x</a>
Functional selectivity, ligand-directed trafficking, conformation-specific agonism: what's in a name?
G-Protein-Coupled/*agonists/*chemistry; Humans; Ligands; Molecular Conformation; Protein Transport; Receptors; Signal Transduction
Research on the design of compounds to selectively affect specific subsets of signals downstream of receptors has burgeoned lately, and several reports discussed at Experimental Biology 2005 indicate progress is being made in the understanding of what makes a drug functionally selective. Different conformations adopted by receptors after associating with specific ligands can determine which intracellular signaling pathways get activated and which do not. The appeal of such specific compounds is enormous when one considers that many disease states might require the subtle manipulation of some (or even one) but not all downstream events stemming from specific receptor activation. Additionally, a better understanding of functional selectivity would likely improve the drug delivery process: if compounds are screened through several functional assays appropriately designed to look for compounds exhibiting a high degree of selectivity, then many potential lead compounds might not be as frequently overlooked.
Simmons Mark A
Molecular interventions
2005
2005-06
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1124/mi.5.3.4" target="_blank" rel="noreferrer noopener">10.1124/mi.5.3.4</a>