1H‐NMR relaxometric studies of interaction between apoptosis specific MRI paramagnetic contrast agents and micellar models of apoptotic cells |
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Authors: | Aurore Van Koninckxloo Céline Henoumont Sophie Laurent Robert N Muller Luce Vander Elst |
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Affiliation: | 1. Department of General, Organic and Biomedical Chemistry, NMR and Molecular Imaging Laboratory, University of Mons, Mons, Belgium;2. CMMI ‐ Center for Microscopy and Molecular Imaging, Gosselies, Belgium |
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Abstract: | 1H‐NMR was previously used to analyze the interaction between peptides (E3 and R826) selected by phage display to target apoptotic cells and phospholipidic models of these cells. In order to avoid the use of apoptotic cells and to obtain a fast evaluation of the efficiency of the potential MRI contrast agents obtained by grafting these peptides and their scramble analogs on a paramagnetic gadolinium complex, their proton relaxometric behavior was investigated in the presence of micelles mimicking healthy and apoptotic cells. Their preferential interaction with 1,2‐dipalmitoyl‐sn‐glycero‐3‐phospho‐l ‐serine micelles mimicking apoptotic cells as compared with 1,2‐dipalmitoyl‐sn‐glycero‐3‐phosphocholine micelles modeling healthy cells was shown by nuclear magnetic relaxation dispersion profiles and the enhancement of the transverse proton relaxation rates at 60 MHz. The association constant values confirm the stronger interaction of the selected conjugated peptides (Ka Gd‐PMN‐E3(gadolinium 2,2′,2′′,2′′′‐((4‐carboxy)pyridine‐2,6‐diyl)bis(methylenenitrilo)]‐tetrakis acetate) grafted with E3 peptide): 2.43 104 m ?1; Ka Gd‐DTPA‐R826(gadolinium ((1‐p‐isothiocyanatobenzyl)‐diethylenetriaminepentaacetate) grafted with R826 peptide): 2.91 104 m ?1) as compared with their conjugated scrambles (Ka Gd‐PMN‐E3sc(gadolinium 2,2′,2′′,2′′′‐((4‐carboxy)pyridine‐2,6‐diyl)bis(methylenenitrilo)]‐tetrakis acetate) grafted with E3 scramble peptide): 0.18 104 m ?1; Ka Gd‐DTPA‐R826sc(gadolinium ((1‐p‐isothiocyanatobenzyl)‐diethylenetriaminepentaacetate) grafted with R826 scramble peptide): 0.32 104 m ?1) even if the conjugation of E3 and R826 seems to decrease their interaction. Copyright © 2015 John Wiley & Sons, Ltd. |
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Keywords: | relaxometry 1H‐NMRD profiles interaction apoptosis contrast agent micellar model |
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