Peptide materials based on the aggregation of poly-phenylalanine conjugates containing gadolinium complexes and acting as potential contrast agents (CAs) in Magnetic Resonance Imaging (MRI) are described. Monomers contain two (F2) or four (F4) phenylalanine residues for self-assembly, a chelating agent, DOTA or DTPA, for achieving gadolinium coordination and ethoxylic linkers at two (L2) or six (L6) PEG units between the chelating group and peptide region. Both DOTA and DTPA tetra-phenylalanine derivatives, and their gadolinium complexes DOTA(Gd)-L6-F4 and DTPA(Gd)-L6-F4, are able to self-aggregate at very low concentration. Structural characterization, obtained by CD and IR measurements, confirms the amyloid type fibril formation in which an antiparallel peptide alignment is preferred. Amyloid type fibril formation was also observed, in solid state, by TEM images and X-ray diffraction patterns. The relaxivity values of DOTA(Gd)-L6-F4 and DTPA(Gd)-L6-F4 and their ability to enhance the MRI cellular response on J774A.1 mouse macrophages cell line indicate that these peptide materials are promising candidate as a new class of supramolecular gadolinium based MRI contrast agents.

Peptide Materials Obtained by Aggregation of Polyphenylalanine Conjugates as Gadolinium-Based Magnetic Resonance Imaging Contrast Agents

DIAFERIA, CARLO;PALLADINO, PASQUALE;ARENA, FRANCESCA;MORELLI, GIANCARLO;ACCARDO, ANTONELLA
2015

Abstract

Peptide materials based on the aggregation of poly-phenylalanine conjugates containing gadolinium complexes and acting as potential contrast agents (CAs) in Magnetic Resonance Imaging (MRI) are described. Monomers contain two (F2) or four (F4) phenylalanine residues for self-assembly, a chelating agent, DOTA or DTPA, for achieving gadolinium coordination and ethoxylic linkers at two (L2) or six (L6) PEG units between the chelating group and peptide region. Both DOTA and DTPA tetra-phenylalanine derivatives, and their gadolinium complexes DOTA(Gd)-L6-F4 and DTPA(Gd)-L6-F4, are able to self-aggregate at very low concentration. Structural characterization, obtained by CD and IR measurements, confirms the amyloid type fibril formation in which an antiparallel peptide alignment is preferred. Amyloid type fibril formation was also observed, in solid state, by TEM images and X-ray diffraction patterns. The relaxivity values of DOTA(Gd)-L6-F4 and DTPA(Gd)-L6-F4 and their ability to enhance the MRI cellular response on J774A.1 mouse macrophages cell line indicate that these peptide materials are promising candidate as a new class of supramolecular gadolinium based MRI contrast agents.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11588/613294
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