title: Self-assembly of PEGylated tetra-phenylalanine derivatives: structural insights from solution and solid state studies.
abstract: Water soluble fibers of PEGylated tetra-phenylalanine (F4), chemically modified at the N-terminus with the DOTA chelating agent, have been proposed as innovative contrast agent (CA) in Magnetic Resonance Imaging (MRI) upon complexation of the gadolinium ion. An in-depth structural characterization of PEGylated F4-fibers, in presence (DOTA-L6-F4) and in absence of DOTA (L6-F4), is reported in solution and at the solid state, by a multiplicity of techniques including CD, FTIR, NMR, DLS, WAXS and SAXS. This study aims to better understand how the aggregation process influences the performance of nanostructures as MRI CAs. Critical aggregation concentrations for L6-F4 (43 μM) and DOTA-L6-F4 (75 μM) indicate that self-aggregation process occurs in the same concentration range, independently of the presence of the CA. The driving force for the aggregation is the π-stacking between the side chains of the aromatic framework. CD, FTIR and WAXS measurements indicate an antiparallel β-sheet organization of the monomers in the resulting fibers. Moreover, WAXS and FTIR experiments point out that in solution the nanomaterials retain the same morphology and monomer organizations of the solid state, although the addition of the DOTA chelating agent affects the size and the degree of order of the fibers.
authors.affiliation: Department of Pharmacy and CIRPeB, University of Naples "Federico II", via Mezzocannone 16, 80134 Napoli, Italy.|Institute of Biostructure and Bioimaging (IBB), CNR, via Mezzocannone 16, 80134 Napoli, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Diaferia
authors.affiliation: Institute of Biostructure and Bioimaging (IBB), CNR, via Mezzocannone 16, 80134 Napoli, Italy.
authors.forename: Flavia Anna
authors.initials: FA
authors.lastname: Mercurio
authors.affiliation: Institute of Crystallography (IC), CNR, Via Amendola 122, 70126 Bari, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Giannini
authors.affiliation: Institute of Crystallography (IC), CNR, Via Amendola 122, 70126 Bari, Italy.
authors.forename: Teresa
authors.initials: T
authors.lastname: Sibillano
authors.affiliation: Department of Pharmacy and CIRPeB, University of Naples "Federico II", via Mezzocannone 16, 80134 Napoli, Italy.|Institute of Biostructure and Bioimaging (IBB), CNR, via Mezzocannone 16, 80134 Napoli, Italy.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Morelli
authors.affiliation: Institute of Biostructure and Bioimaging (IBB), CNR, via Mezzocannone 16, 80134 Napoli, Italy.
authors.forename: Marilisa
authors.initials: M
authors.lastname: Leone
authors.affiliation: Department of Pharmacy and CIRPeB, University of Naples "Federico II", via Mezzocannone 16, 80134 Napoli, Italy.|Institute of Biostructure and Bioimaging (IBB), CNR, via Mezzocannone 16, 80134 Napoli, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Accardo