Cross-beta nanostructures based on dinaphthylalanine Gd-conjugates loaded with doxorubicin(172 visite) Diaferia C, Gianolio E, Sibillano T, Mercurio FA, Leone M, Giannini C, Balasco N, Vitagliano L, Morelli G, Accardo A
*** IBB - CNR *** Department of Pharmacy, Research Centre on Bioactive Peptides (CIRPeB), University of Naples "Federico II", Via Mezzocannone 16, 80134, Naples, Italy., Department of Molecular Biotechnologies and Health Science, University of Turin, Via Nizza 52, 10125, Turin, Italy., Institute of Crystallography (IC), CNR, Via Amendola 122, 70126, Bari, Italy., Institute of Biostructure and Bioimaging (IBB), CNR, via Mezzocannone 16, 80134, Naples, Italy., Department of Pharmacy, Research Centre on Bioactive Peptides (CIRPeB), University of Naples "Federico II", Via Mezzocannone 16, 80134, Naples, Italy. antonella.accardo@unina.it.,
Riferimenti:
Non disponibile.
Very recently we proposed novel di- and tetra-phenylalanine peptides derivatized with gadolinium complexes as potentials supramolecular diagnostic agents for applications in MRI (Magnetic Resonance Imaging). It was observed that in very short FF dipeptide building blocks, the propensity to aggregate decreases significantly after modification with bulky moiety such as Gd-complexes, thus limiting their potential as CAs. We hypothesized that the replacement of the Phe side chain with more extended aromatic groups could improve the self-assembling. Here we describe the synthesis, structural and relaxometric behavior of a novel water soluble self-assembled peptide CA based on 2-naphthylalanine (2Nal). The peptide conjugate Gd-DOTA-L6-(2Nal)2 is able to self-assemble in long fibrillary nanostructures in water solution (up to 1.0 mg/mL). CD and FTIR spectroscopies indicate a beta sheet secondary structure with an antiparallel orientation of single strands. All data are in good agreement with WAXS and SAXS characterizations that show the typical "cross-beta pattern" for fibrils at the solid state. Molecular modeling indicates the three-dimensional structure of the peptide spine of aggregates is essentially constituted by extended beta-sheet motifs stabilized by hydrogen bonds and hydrophobic interactions. The high relaxivity of nanoaggregates (12.3 mM-1 s-1 at 20 MHz) and their capability to encapsulate doxorubicin suggest their potential application as supramolecular theranostic agents.
81 Records (75 escludendo Abstract e Conferenze). Impact factor totale: 309.075 (294.938 escludendo Abstract e Conferenze). Impact factor a 5 anni totale: 319.4 (304.811 escludendo Abstract e Conferenze).
ibb.cnr.it