Micelles obtained by aggregation of gemini surfactants containing the CCK8 peptide and a gadolinium complex.
Two gemini surfactants, [C18CysL5CCK8](2) and [C18CysDTPAGlu](2), containing, respectively, the CCK8 peptide and the DTPAGlu chelating agent or its gadolinium complex have been prepared by linking lipophilic chains through a disulfide bond between two cysteine residues. The two surfactants aggregate in water solution forming pure or mixed micelles, with a critical micellar concentration in the 5 x 10(-6)-5 x 10(-5) mol kg(-1) range, as measured by fluorescence spectroscopy. As indicated by small-angle neutron scattering, the shape and size of the micelles are influenced by the temperature: increasing temperature leads to progressive reduction of the size of the supramolecular aggregates. Cylindrical structures found at lower temperatures (10-40 degrees C) evolve into ellipsoidal micelles at 50-80 degrees C. Furthermore, the surface-exposed CCK8 peptide changes its conformation above a transition temperature of approximately 45 degrees C, going from a beta-sheet to a random-coil structure, as indicated by circular dichroism measurements. The mixed aggregate obtained by coaggregation of the two gemini-based amphiphilic compounds, [C18CysDTPAGlu(Gd)](2) and [C18CysL5CCK8](2) in 70:30 molar ratio, represents the first example of a peptide-containing gemini surfactant as a potential target-selective contrast agent in MRI. In fact, it presents a high relaxivity value of the gadolinium complex, 21.5 mM(-1) s(-1), and the CCK8 bioactive peptide exposed on the external surface is therefore capable of selective targeting of the cholecystokinin receptors.
Accardo
Antonella
A
Department of Biological Sciences and IBB CNR, CIRPeB, University of Naples Federico II, Naples, Italy.
Tesauro
Diego
D
Morisco
Anna
A
Mangiapia
Gaetano
G
Vaccaro
Mauro
M
Gianolio
Eliana
E
Heenan
Richard K
RK
Paduano
Luigi
L
Morelli
Giancarlo
G
D002766:Cholecystokinin / Q000138:chemical synthesis / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D005682:Gadolinium / Q000737:chemistry*; D008823:Micelles; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011487:Protein Conformation; D013501:Surface-Active Agents / Q000138:chemical synthesis / Q000737:chemistry*
D008823:Micelles; D010446:Peptide Fragments; D013501:Surface-Active Agents; C410885:cholecystokinin 8; D002766:Cholecystokinin; D005682:Gadolinium