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Micelles derivatized with octreotide as potential target‐selective contrast agents in MRI
Author(s) -
Morisco Anna,
Accardo Antonella,
Gianolio Eliana,
Tesauro Diego,
Benedetti Ettore,
Morelli Giancarlo
Publication year - 2009
Publication title -
journal of peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 66
eISSN - 1099-1387
pISSN - 1075-2617
DOI - 10.1002/psc.1087
Subject(s) - gadolinium , micelle , chemistry , dota , circular dichroism , mri contrast agent , peptide , amphiphile , monomer , chelation , stereochemistry , copolymer , organic chemistry , aqueous solution , biochemistry , polymer
New amphiphilic monomers (OCA‐DTPAGlu and OCA‐DOTA) containing, in the same molecule, three different functions: (i) the chelating agent (DTPAGlu or DOTA) able to coordinate gadolinium ion, (ii) the octreotide bioactive peptide able to target somatostatin receptors, and (iii) a hydrophobic moiety with two 18‐carbon atoms alkyl chains have been designed and synthesized by solid‐phase methods. The novel amphiphilic monomers aggregate, in water solution, giving stable micelles at very low concentration (cmc values of 2.3 × 10 −6 mol kg −1 and 2.5 × 10 −6 mol kg −1 for OCA‐DTPAGlu and OCA‐DOTA, respectively) as confirmed by fluorescence spectroscopy. Fluorescence studies and circular dichroism experiments indicate, for the two compounds as well as for their gadolinium complexes (OCA‐DOTA(Gd) and OCA‐DTPAGlu(Gd)), the complete exposure of octreotide on the micelle surface, and the predominant presence of an antiparallel β‐sheet peptide conformation characterized by a β‐like turn. The high relaxivity value ( r 1 p = 13.9 m M −1 s −1 at 20 MHz and 25 °C), measured for micelles obtained by the gadolinium complex OCA‐DTPAGlu(Gd), indicates these aggregates as promising target‐selective magnetic resonance imaging (MRI) contrast agents. Copyright © 2008 European Peptide Society and John Wiley & Sons, Ltd.