| 1. |
- Accardo, Antonella, et al.
(författare)
-
High-relaxivity supramolecular aggregates containing peptides and Gd complexes as contrast agents in MRI
- 2007
-
Ingår i: Journal of Biological Inorganic Chemistry. - : Springer Science and Business Media LLC. - 1432-1327 .- 0949-8257. ; 12:2, s. 267-276
-
Tidskriftsartikel (refereegranskat)abstract
- Mixed supramolecular aggregates, obtained by assembling together two amphiphilic monomers (C18H37)2NCO(CH2)2CO(AdOO)5-G-CCK8 (AdOO is 8-amino-3,6-dioxaoctanoic acid, CCK8 is C-terminal octapeptide of cholecystokinin) and (C18H37)2NCO(CH2)2COLys(DTPAGlu)CONH2 (DTPAGlu is N,N-bis[2-[bis(carboxyethyl)amino]ethyl]-l-glutamic acid), are characterized for their structural parameters by dynamic light scattering and for their relaxometric properties, in the absence and in the presence of 0.9 wt% NaCl. Two different aggregates (micelles and bilayer structures) are present in the absence of NaCl, while only bilayer structures are observed at physiological ionic strength. The presence of NaCl increases the ionic strength, promoting a decrease in the repulsions between the polar heads and among the aggregates in solution, thus supporting the formation of large-curvature aggregates such as bilayer structures like vesicles. In these conditions the closed, vesicular shape and the large size (hydrodynamic radius of about 300 Å) of the aggregates allow a high number of paramagnetic gadolinium complexes and bioactive peptides to be accommodated on the inner and external surfaces . The presence of the salt causes a variation in the structural arrangement of the molecules and a partial rigidification of the assembled Gd(III) complexes on the surface vesicles, reducing their internal motions and giving an approximately 15% higher relaxivity value (r 1p = 21.0 and 18.6 Mm−1 s−1 in the presence and in the absence of NaCl, respectively). The vesicles obtained, for the high relaxivity of each gadolidium complex and for the presence of a surface-exposed bioactive peptide, are very promising candidates as target-selective MRI contrast agents.
|
|
| 2. |
- Tesauro, Diego, et al.
(författare)
-
Peptide Derivatized Lamellar Aggregates as Target-Specific MRI Contrast Agents
- 2007
-
Ingår i: ChemBioChem. - : Wiley. - 1439-4227 .- 1439-7633. ; 8:8, s. 950-955
-
Tidskriftsartikel (refereegranskat)abstract
- The relaxivity behaviour and the structural characterization of new supramolecular aggregates (bilayer structures and micelles) obtained by combining two different amphiphilic monomers are reported. One monomer, (C18)2DTPAGlu-Gd, contains a very stable gadolinium complex, and the other, DSPE-PEG2000-CCK8, contains the bioactive CCK8 peptide. Samples that contained only DSPE-PEG2000-CCK8, or up to 50 % (C18)2DTPAGlu-Gd, aggregated as double-layer structures (lamellar aggregates) with a thickness of80-100 Å, as evaluated by SANS measurement and Cryo-TEM imaging. A transition to micelle formation was observed when the amount of (C18)2DTPAGlu-Gd in the aggregate was increased. These were rod-like micelles 40 Å in radius and >200 Å in length. The proton relaxivities for both lamellar aggregates and rod-like micelles were the same (17.2 mM-1 s-1), although the values were the results of different combinations of local and global contributions. The in vitro target selectivity of aggregates that contained the CCK-8 peptide was demonstrated by using nuclear medicine techniques.
|
|
