Delia Picone

Professor of General and Inorganic Chemistry

Name Delia
Surname Picone
Institution University of Naples – Federico II
Address Department of Chemical Sciences, University of Naples Federico II, Complesso Universitario di Monte Sant'Angelo, Via Cintia, I-80126 Napoli, Italy
Delia Picone


  • A preliminary study on the application of natural sweet proteins in agar-based gels.

    Publication Date: 01/04/2017 on Journal of texture studies
    by Miele NA, Di Monaco R, Dell'Amura F, Rega MF, Picone D, Cavella S
    DOI: 10.1111/jtxs.12215

    Natural sweet proteins may be used as sugar replacer in simple liquid food systems but their applicability in more complex matrices has not been investigated yet. Gelling agent nature and texture characteristics as well as type and distribution of a stimulus in a gel could affect taste perception through inhibition or enhancement of tastants migration to the receptors. The mechanical, nonoral texture and time-intensity sweetness characteristics of sweet proteins MNEI and super sweet Y65R mutant, aspartame and saccharin added at a concentration iso-sweet to 40 g/L of sucrose in three agar gel concentrations (1%, 1.5%, and 2%) were evaluated. The results have shown that agar concentration and agar sweetener interaction particularly affect mechanical fracture stress and non oral hardness of the sweetened gels. Time intensity results illustrated that unlike in solution, the intensity of sweet taste in a gelled system over time decreases. Indeed, the behavior of the sweet proteins differed greatly in the gelled system compared to when they are in solution.

  • Hot spot mapping of protein surfaces with TEMPOL: Bovine pancreatic RNase A as a model system.

    Publication Date: 01/02/2017 on Biochimica et biophysica acta
    by Niccolai N, Morandi E, Gardini S, Costabile V, Spadaccini R, Crescenzi O, Picone D, Spiga O, Bernini A
    DOI: 10.1016/j.bbapap.2016.11.014

    TEMPOL spin-label has been used to identify surface exposure of protein nuclei from NMR analysis of the induced paramagnetic relaxation enhancements (PRE). The absence of linear dependence between atom depths and observed PRE reveals that specific mechanisms drive the approach of the paramagnet to the protein surface. RNase A represents a unique protein system to explore the fine details of the information offered by TEMPOL induced PRE, due to the abundance of previous results, obtained in solution and in the crystal, dealing with surface dynamics behavior of this protein. MD simulations in explicit solvent have been performed, also in the presence of TEMPOL, in order to delineate the role of intermolecular hydrogen bonds (HB) on PRE extents. Comparison of our results with the ones obtained from multiple solvent crystal structure (MSCS) studies yields information on the specificities that these two techniques have for characterizing protein-ligand interactions, a fundamental step in the development of reliable surface druggability predictors.

  • NMR Spectroscopic Assignment of Backbone and Side-Chain Protons in Fully Protonated Proteins: Microcrystals, Sedimented Assemblies, and Amyloid Fibrils.

    Publication Date: 12/12/2016 on Angewandte Chemie (International ed. in English)
    by Stanek J, Andreas LB, Jaudzems K, Cala D, Lalli D, Bertarello A, Schubeis T, Akopjana I, Kotelovica S, Tars K, Pica A, Leone S, Picone D, Xu ZQ, Dixon NE, Martinez D, Berbon M, El Mammeri N, Noubhani A, Saupe S, Habenstein B, Loquet A, Pintacuda G
    DOI: 10.1002/anie.201607084

    We demonstrate sensitive detection of alpha protons of fully protonated proteins by solid-state NMR spectroscopy with 100-111 kHz magic-angle spinning (MAS). The excellent resolution in the Cα-Hα plane is demonstrated for 5 proteins, including microcrystals, a sedimented complex, a capsid and amyloid fibrils. A set of 3D spectra based on a Cα-Hα detection block was developed and applied for the sequence-specific backbone and aliphatic side-chain resonance assignment using only 500 μg of sample. These developments accelerate structural studies of biomolecular assemblies available in submilligram quantities without the need of protein deuteration.

  • Influence of pH on the structure and stability of the sweet protein MNEI.

    Publication Date: 01/10/2016 on FEBS letters
    by Spadaccini R, Leone S, Rega MF, Richter C, Picone D
    DOI: 10.1002/1873-3468.12437

    MNEI is a single-chain derivative of the sweet protein monellin that, in recent years, has become an accepted model for studying protein dynamic properties such as folding and aggregation. Although MNEI is very resistant at acidic pH, exposure to neutral or alkaline pH strongly affects its stability. We have performed a thorough NMR study of the dynamic properties of MNEI at different pHs. The results demonstrate that, at physiological temperature, exposure to higher pH increases MNEI flexibility. The changes, originating from a well-defined region in the protein, are transmitted to the whole structure and are likely to be the key for triggering unfolding processes.

  • Sweeter and stronger: enhancing sweetness and stability of the single chain monellin MNEI through molecular design.

    Publication Date: 23/09/2016 on Scientific reports
    by Leone S, Pica A, Merlino A, Sannino F, Temussi PA, Picone D
    DOI: 10.1038/srep34045

    Sweet proteins are a family of proteins with no structure or sequence homology, able to elicit a sweet sensation in humans through their interaction with the dimeric T1R2-T1R3 sweet receptor. In particular, monellin and its single chain derivative (MNEI) are among the sweetest proteins known to men. Starting from a careful analysis of the surface electrostatic potentials, we have designed new mutants of MNEI with enhanced sweetness. Then, we have included in the most promising variant the stabilising mutation E23Q, obtaining a construct with enhanced performances, which combines extreme sweetness to high, pH-independent, thermal stability. The resulting mutant, with a sweetness threshold of only 0.28 mg/L (25 nM) is the strongest sweetener known to date. All the new proteins have been produced and purified and the structures of the most powerful mutants have been solved by X-ray crystallography. Docking studies have then confirmed the rationale of their interaction with the human sweet receptor, hinting at a previously unpredicted role of plasticity in said interaction.

  • Molecular Dynamics Driven Design of pH-Stabilized Mutants of MNEI, a Sweet Protein.

    Publication Date: 24/06/2016 on PloS one
    by Leone S, Picone D
    DOI: 10.1371/journal.pone.0158372

    MNEI is a single chain derivative of monellin, a plant protein that can interact with the human sweet taste receptor, being therefore perceived as sweet. This unusual physiological activity makes MNEI a potential template for the design of new sugar replacers for the food and beverage industry. Unfortunately, applications of MNEI have been so far limited by its intrinsic sensitivity to some pH and temperature conditions, which could occur in industrial processes. Changes in physical parameters can, in fact, lead to irreversible protein denaturation, as well as aggregation and precipitation. It has been previously shown that the correlation between pH and stability in MNEI derives from the presence of a single glutamic residue in a hydrophobic pocket of the protein. We have used molecular dynamics to study the consequences, at the atomic level, of the protonation state of such residue and have identified the network of intramolecular interactions responsible for MNEI stability at acidic pH. Based on this information, we have designed a pH-independent, stabilized mutant of MNEI and confirmed its increased stability by both molecular modeling and experimental techniques.

  • Preferential interaction of the Alzheimer peptide Aβ-(1-42) with Omega-3-containing lipid bilayers: structure and interaction studies.

    Publication Date: 01/02/2016 on FEBS letters
    by Emendato A, Spadaccini R, De Santis A, Guerrini R, D'Errico G, Picone D
    DOI: 10.1002/1873-3468.12082

    Many age-related neurodegenerative diseases, including Alzheimer Disease (AD), are elicited by an interplay of genetic, environmental, and dietary factors. Food rich in Omega-3 phospholipids seems to reduce the AD incidence. To investigate the molecular basis of this beneficial effect, we have investigated by CD and ESR studies the interaction between the Alzheimer peptide Aβ-(1-42) and biomimetic lipid bilayers. The inclusion of 1,2-didocosahexaenoyl-sn-glycero-3-phosphocholine does not change significantly the bilayers organization, but favors its Aβ-(1-42) interaction. The Omega-3 lipid amount modulates the effect intensity, suggesting a peptide selectivity for membranes containing polyunsatured fatty acids (PUFA) and providing hints for the mechanism and therapy of AD.

  • Acetate: friend or foe? Efficient production of a sweet protein in Escherichia coli BL21 using acetate as a carbon source.

    Publication Date: 25/07/2015 on Microbial cell factories
    by Leone S, Sannino F, Tutino ML, Parrilli E, Picone D
    DOI: 10.1186/s12934-015-0299-0

    Escherichia coli is, to date, the most used microorganism for the production of recombinant proteins and biotechnologically relevant metabolites. High density cell cultures allow efficient biomass and protein yields. However, their main limitation is the accumulation of acetate as a by-product of unbalanced carbon metabolism. Increased concentrations of acetate can inhibit cellular growth and recombinant protein production, and many efforts have been made to overcome this problem. On the other hand, it is known that E. coli is able to grow on acetate as the sole carbon source, although this mechanism has never been employed for the production of recombinant proteins.

  • Platinated oligomers of bovine pancreatic ribonuclease: Structure and stability.

    Publication Date: 01/05/2015 on Journal of inorganic biochemistry
    by Picone D, Donnarumma F, Ferraro G, Russo Krauss I, Fagagnini A, Gotte G, Merlino A
    DOI: 10.1016/j.jinorgbio.2015.02.011

    The reaction between cis-diamminedichloroplatinum(II) (CDDP), cisplatin, a common anticancer drug, and bovine pancreatic ribonuclease (RNase A), induces extensive protein aggregation, leading to the formation of one dimer, one trimer and higher oligomers whose yields depend on cisplatin/protein ratio. Structural and functional properties of the purified platinated species, together with their spontaneous dissociation and thermally induced denaturation, have been characterized. Platinated species preserve a significant, although reduced, ribonuclease activity. The high resistance of the dimers against dissociation and the different thermal unfolding profiles suggest a quaternary structure different from those of the well-known swapped dimers of RNase A.

  • Design of sweet protein based sweeteners: hints from structure-function relationships.

    Publication Date: 15/04/2015 on Food chemistry
    by Rega MF, Di Monaco R, Leone S, Donnarumma F, Spadaccini R, Cavella S, Picone D
    DOI: 10.1016/j.foodchem.2014.10.151

    Sweet proteins represent a class of natural molecules, which are extremely interesting regarding their potential use as safe low-calories sweeteners for individuals who need to control sugar intake, such as obese or diabetic subjects. Punctual mutations of amino acid residues of MNEI, a single chain derivative of the natural sweet protein monellin, allow the modulation of its taste. In this study we present a structural and functional comparison between MNEI and a sweeter mutant Y65R, containing an extra positive charge on the protein surface, in conditions mimicking those of typical beverages. Y65R exhibits superior sweetness in all the experimental conditions tested, has a better solubility at mild acidic pH and preserves a significant thermal stability in a wide range of pH conditions, although slightly lower than MNEI. Our findings confirm the advantages of structure-guided protein engineering to design improved low-calorie sweeteners and excipients for food and pharmaceutical preparations.