Concetta Giancola

Professor of Physical Chemistry

Name Concetta
Surname Giancola
Institution University of Naples – Federico II
Address Department of Pharmacy, University of Napoli Federico II, Via D. Montesano 49, 80131, Napoli, Italy; InterUniversity Center for Research in Neurosciences, University of Campania "Luigi Vanvitelli", Napoli, Italy
Concetta Giancola


  • Huntingtin protein: A new option for fixing the Huntington's disease countdown clock.

    Publication Date: 08/03/2018 on Neuropharmacology
    by Caterino M, Squillaro T, Montesarchio D, Giordano A, Giancola C, Melone MAB
    DOI: 10.1016/j.neuropharm.2018.03.009

    Huntington's disease is a dreadful, incurable disorder. It springs from the autosomal dominant mutation in the first exon of the HTT gene, which encodes for the huntingtin protein (HTT) and results in progressive neurodegeneration. Thus far, all the attempted approaches to tackle the mutant HTT-induced toxicity causing this disease have failed. The mutant protein comes with the aberrantly expanded poly-glutamine tract. It is primarily to blame for the build-up of β-amyloid-like HTT aggregates, deleterious once broadened beyond the critical ∼35-37 repeats threshold. Recent experimental findings have provided valuable information on the molecular basis underlying this HTT-driven neurodegeneration. These findings indicate that the poly-glutamine siding regions and many post-translation modifications either abet or counter the poly-glutamine tract. This review provides an overall, up-to-date insight into HTT biophysics and structural biology, particularly discussing novel pharmacological options to specifically target the mutated protein and thus inhibit its functions and toxicity.

  • Binding of Harmine Derivatives to DNA: A Spectroscopic Investigation.

    Publication Date: 27/10/2017 on Molecules (Basel, Switzerland)
    by Pagano B, Caterino M, Filosa R, Giancola C
    DOI: 10.3390/molecules22111831

    Harmine belongs to a group of β-carboline alkaloids endowed with antitumor properties. Harmine and its derivatives are thought to bind to DNA and interfere with topoisomerase activities. We investigated the base-dependent binding of harmine, and three of its synthetic anticancer-active derivatives to the genomic DNA from calf thymus and two synthetic 20-mer double helices, the poly(dG-dC)·poly(dG-dC) and the poly(dA-dT)·poly(dA-dT), by means of UV-Vis and circular dichroism (CD) spectroscopies. The data show that the DNA binding and stabilising properties of the investigated derivatives are base pair-dependent. These results could be used as a guide to design and develop further bioactive analogues.

  • Not unusual, just different! Chemistry, biology and applications of G-quadruplex nucleic acids.

    Publication Date: 01/05/2017 on Biochimica et biophysica acta
    by Giancola C, Montesarchio D
    DOI: 10.1016/j.bbagen.2017.03.022
  • Tandem application of ligand-based virtual screening and G4-OAS assay to identify novel G-quadruplex-targeting chemotypes.

    Publication Date: 24/01/2017 on Biochimica et biophysica acta
    by Musumeci D, Amato J, Zizza P, Platella C, Cosconati S, Cingolani C, Biroccio A, Novellino E, Randazzo A, Giancola C, Pagano B, Montesarchio D
    DOI: 10.1016/j.bbagen.2017.01.024

    G-quadruplex (G4) structures are key elements in the regulation of cancer cell proliferation and their targeting is deemed to be a promising strategy in anticancer therapy.

  • Energetics of ligand-receptor binding affinity on endothelial cells: An in vitro model.

    Publication Date: 01/08/2016 on Colloids and surfaces. B, Biointerfaces
    by Fotticchia I, Guarnieri D, Fotticchia T, Falanga AP, Vecchione R, Giancola C, Netti PA
    DOI: 10.1016/j.colsurfb.2016.04.018

    Targeted therapies represent a challenge in modern medicine. In this contest, we propose a rapid and reliable methodology based on Isothermal Titration Calorimetry (ITC) coupled with confluent cell layers cultured around biocompatible templating microparticles to quantify the number of overexpressing receptors on cell membrane and study the energetics of receptor-ligand binding in near-physiological conditions. In the in vitro model here proposed we used the bEnd3 cell line as brain endothelial cells to mimic the blood brain barrier (BBB) cultured on dextran microbeads ranging from 67μm to 80μm in size (Cytodex) and the primary human umbilical vein cells (HUVEC) for comparison. The revealed affinity between transferrin (Tf) and transferrin receptor (TfR) in both systems is very high, Kd values are in the order of nM. Conversely, the value of TfRs/cell reveals a 100-fold increase in the number of TfRs per bEnd3 cells compared to HUVEC cells. The presented methodology can represent a novel and helpful strategy to identify targets, to address drug design and selectively deliver therapeutics that can cross biological barriers such as the blood brain barrier.

  • Cyclodextrin-assisted assembly of PEGylated polyester nanoparticles decorated with folate.

    Publication Date: 01/05/2016 on Colloids and surfaces. B, Biointerfaces
    by Conte C, Fotticchia I, Tirino P, Moret F, Pagano B, Gref R, Ungaro F, Reddi E, Giancola C, Quaglia F
    DOI: 10.1016/j.colsurfb.2016.01.035

    In the last decades, nano-oncologicals bearing a polyethylene glycol (PEG) coating are being emerging as biomimetic devices able to drive their drug cargo to solid tumors through passive mechanisms. To improve selectivity toward cancer cells, nanocarriers decorated with the small ligand folate have been widely investigated. Nevertheless, a great challenge remains the effective exposition of folate on nanoparticles (NPs), which is a key prerequisite to ensure the correct binding to receptor and the following endocytic uptake. On these premises, in this study we propose a novel strategy to produce core-shell folate-targeted NPs based on diblock copolymers of poly(ε-caprolactone) (PCL) and PEG through the aid of (2-hydroxypropyl)-β-cyclodextrin (HPβCD). PCL4300-PEG2000 and PCL4300-PEG2000-Fol copolymers were synthesized, characterized and employed to produce NPs without and with HPβCD by a melting/sonication procedure. Colloidal properties of targeted NPs produced with HPβCD demonstrated a highly extended conformation of PEG chains in the shell, an enhanced interaction with a specific antibody against folate and a higher uptake in cells overexpressing folate receptor. Overall, these results suggest that proper manipulation of PEG shell conformation through HPβCD can represent a novel non-covalent strategy to modify shell features.

  • The oxidative damage to the human telomere: effects of 5-hydroxymethyl-2'-deoxyuridine on telomeric G-quadruplex structures.

    Publication Date: 21/07/2015 on Organic & biomolecular chemistry
    by Virgilio A, Esposito V, Mayol L, Giancola C, Petraccone L, Galeone A
    DOI: 10.1039/c5ob00748h

    As part of the genome, human telomeric regions can be damaged by the chemically reactive molecules responsible for oxidative DNA damage. Considering that G-quadruplex structures have been proven to occur in human telomere regions, several studies have been devoted to investigating the effect of oxidation products on the properties of these structures. However only investigations concerning the presence in G-quadruplexes of the main oxidation products of deoxyguanosine and deoxyadenosine have appeared in the literature. Here, we investigated the effects of 5-hydroxymethyl-2'-deoxyuridine (5-hmdU), one of the main oxidation products of T, on the physical-chemical properties of the G-quadruplex structures formed by two human telomeric sequences. Collected calorimetric, circular dichroism and electrophoretic data suggest that, in contrast to most of the results on other damage, the replacement of a T with a 5-hmdU results in only negligible effects on structural stability. Reported results and other data from literature suggest a possible protecting effect of the loop residues on the other parts of the G-quadruplexes.

  • Thermodynamic signature of secondary nano-emulsion formation by isothermal titration calorimetry.

    Publication Date: 09/12/2014 on Langmuir : the ACS journal of surfaces and colloids
    by Fotticchia I, Fotticchia T, Mattia CA, Netti PA, Vecchione R, Giancola C
    DOI: 10.1021/la503558w

    The stabilization of oil in water nano-emulsions by means of a polymer coating is extremely important; it prolongs the shelf life of the product and makes it suitable for a variety of applications ranging from nutraceutics to cosmetics and pharmaceutics. To date, an effective methodology to assess the best formulations in terms of thermodynamic stability has yet to be designed. Here, we perform a complete physicochemical characterization based on isothermal titration calorimetry (ITC) compared to conventional dynamic light scattering (DLS) to identify polymer concentration domains that are thermodynamically stable and to define the degree of stability through thermodynamic functions depending upon any relevant parameter affecting the stability itself, such as type of polymer coating, droplet distance, etc. For instance, the method was proven by measuring the energetics in the case of two different biopolymers, chitosan and poly-L-lysine, and for different concentrations of the emulsion coated with poly-L-lysine.

  • G-quadruplex on oligo affinity support (G4-OAS): an easy affinity chromatography-based assay for the screening of G-quadruplex ligands.

    Publication Date: 06/05/2014 on Analytical chemistry
    by Musumeci D, Amato J, Randazzo A, Novellino E, Giancola C, Montesarchio D, Pagano B
    DOI: 10.1021/ac500444m

    A simple, cheap, and highly reproducible affinity chromatography-based method has been developed for the screening of G-quadruplex binders. The tested compounds were flowed through a polystyrene resin functionalized with an oligonucleotide able to form, in proper conditions, a G-quadruplex structure. Upon cation-induced control of the folding/unfolding processes of the immobilized G-quadruplex-forming sequence, small molecules specifically interacting with the oligonucleotide structure were first captured and then released depending on the used working solution. This protocol, first optimized for different kinds of known G-quadruplex ligands and then applied to a set of putative ligands, has allowed one to fully reuse the same functionalized resin batch, recycled for several tens of experiments without loss in efficiency and reproducibility.

  • PNA as a potential modulator of COL7A1 gene expression in dominant dystrophic epidermolysis bullosa: a physico-chemical study.

    Publication Date: 01/12/2013 on Molecular bioSystems
    by Amato J, Stellato MI, Pizzo E, Petraccone L, Oliviero G, Borbone N, Piccialli G, Orecchia A, Bellei B, Castiglia D, Giancola C
    DOI: 10.1039/c3mb70283a

    Dominant diseases are single gene disorders occurring in the heterozygous state. The mutated allele exerts a dominant effect because it produces an abnormal polypeptide that interferes with the function of the normal allele product. Peptide Nucleic Acids (PNAs) offer a route for a potential therapy for dominant diseases by selectively silencing the allele carrying the dominant mutation. Here, we have synthesized and studied the properties of a 15-mer PNA fully complementary to the site of the c.5272-38T>A sequence variation, which identifies a recurrent mutant COL7A1 allele causing dominant dystrophic epidermolysis bullosa (DDEB), a mendelian disease characterized by skin blistering. The PNA was conjugated with four lysine residues at the C-terminus and a fluorescent probe at the N-terminus. Physico-chemical results proved the formation of a stable, selective PNA/mutant-DNA heteroduplex in vitro. Intriguingly, when transfected into normal human fibroblasts, the PNA correctly localized in the cell nucleus. Our results open new therapeutic possibilities for patients with DDEB.