Abstract
The delivery of drugs involving bioactive peptides and proteins from water to natural cell membranes is crucial as aprimary step of the biological action. Lipid bilayer membrane, as a platform of vital functions, is a dynamic structurewhere molecules are always fluctuating under physiological conditions. The mechanism of drug deliveries is relatedto the molecular dynamics in such soft, fluid membrane interface. To gain insight into molecular mechanisms of drug deliveries in a noninvasive manner, we develop the method tomonitor dynamic properties of drugs and lipid components in membranes without labeled nuclei, by applying multi-nuclear high–resolution solution NMR in combination with the pulsed–field–gradient technique. The simultaneousobservation of membrane–bound and free drugs in situenables us to quantify i)in what amount the drug is bound insituand ii)how fast the drug is moving within the membrane, in relation to the thermal fluctuation of the soft, fluidenvironment. Finally, the method is extended to the in–cell NMR spectroscopy to detect the real–time uptake ofbioactive peptides with minimal perturbation.
