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


  • Solution structure of nociceptin peptides.

    Publication Date: 01/09/2002 on Journal of peptide science : an official publication of the European Peptide Society
    by Amodeo P, Guerrini R, Picone D, Salvadori S, Spadaccini R, Tancredi T, Temussi PA
    DOI: 10.1002/psc.412

    Peptides embedded in the sequence of pre-pro-nociceptin, i.e. nociceptin, nocistatin and orphanin FQ2, have shed light on the complexity of the mechanisms involving the peptide hormones related to pain and have opened up new perspectives for the clinical treatment of pain. The design of new ligands with high selectivity and bioavailability, in particular for ORL1, is important both for the elucidation and control of the physiological role of the receptor and for their therapeutic importance. The failure to obtain agonists and antagonists when using, for nociceptin, the same substitutions that are successful for opioids, and the conformational flexibility of them all, justify systematic efforts to study the solution conformation under conditions as close as possible to their natural environment. Structural studies of linear peptides in solution are hampered by their high flexibility. A direct structural study of the complex between a peptide and its receptor would overcome this difficulty, but such a study is not easy since opioid receptors are membrane proteins. Thus, conformational studies of lead peptides in solution are still important for drug design. This review deals with conformational studies of natural pre-nociceptin peptides in several solvents that mimic in part the different environments in which the peptides exert their action. None of the structural investigations yielded a completely reliable bioactive conformation, but the global conformation of the peptides in biomimetic environments can shed light on their interaction with receptors.

  • Environmental mimic of receptor interaction: conformational analysis of CCK-15 in solution.

    Publication Date: 14/02/2002 on Journal of medicinal chemistry
    by Albrizio S, Carotenuto A, Fattorusso C, Moroder L, Picone D, Temussi PA, D'Ursi A

    CCK-15, a peptide derived from the 115-membered CCK preprohormone, was the object of a comparative conformational analysis by NMR spectroscopy and molecular modeling methods. NMR data in several solvents demonstrate that the propensity of the peptide to fold into a helical conformation is intrinsic, not merely a consequence of the interaction with phosphatidylcholine micelles or with a putative receptor, as suggested by a previous study on CCK-8 (Pellegrini, M.; Mierke, D. Biochemistry 1999, 38, 14775-14783.). The prevailing CCK-15 conformer in a mixture 1,1,1,3,3,3-hexafluoroacetone/water reveals that the residues common to CCK-15 and CCK-8 assume very similar conformations. Our CCK-15 structure is consistent with the model of receptor interaction proposed by Pellegrini and Mierke and discloses possible novel interactions that involve a larger area of the putative receptor. The consensus structure between CCK-15 and CCK-8 shows a good superposition of the side chains of residues 12-14 with crucial moieties of two non-peptidic CCK-A antagonists.

  • Bacterial expression and conformational analysis of a chemosensory protein from Schistocerca gregaria.

    Publication Date: 01/09/2001 on European journal of biochemistry
    by Picone D, Crescenzi O, Angeli S, Marchese S, Brandazza A, Ferrara L, Pelosi P, Scaloni A

    Chemosensory proteins (CSPs) are a class of small, soluble proteins present at high concentrations in chemosensory organs of different insect species. Several pieces of evidence suggest their involvement in carrying chemical messages from the environment to chemosensory receptors. However, a structural description of the mechanism of delivery has not been reported. In order to provide the first detailed conformational characterization of these molecules, we cloned a specific isoform (CSP-sg4) from Schistocerca gregaria and expressed it in Escherichia coli. The product was obtained with yields of more than 20 mg per L of culture, all in its soluble form. The recombinant protein was identical to the native one with respect to pairing of the disulfide bridges, aggregative state and secondary structure elements. Structural investigations revealed a significantly stable polypeptide with respect to variations in temperature and acidity. CD analysis, preliminary NMR data and secondary structure prediction pointed to a correctly folded structure where helical regions and loops are alternated in a similar fashion as that observed for other classes of odorant- and pheromone-binding proteins presenting no sequence similarity to CSPs.

  • 1H and 15N sequential assignment and secondary structure of the monomeric N67D mutant of bovine seminal ribonuclease.

    Publication Date: 01/07/2001 on Journal of biomolecular NMR
    by Crescenzi O, Carotenuto A, D'Ursi AM, Tancredi T, D'Alessio G, Avitabile F, Picone D
  • Peptide T revisited: conformational mimicry of epitopes of anti-HIV proteins.

    Publication Date: 01/04/2001 on Journal of peptide science : an official publication of the European Peptide Society
    by Picone D, Rivieccio A, Crescenzi O, Caliendo G, Santagada V, Perissutti E, Spisani S, Traniello S, Temussi PA
    DOI: 10.1002/psc.320

    Peptide T (ASTTTNYT), a fragment corresponding to residues 185-192 of gp120, the coat protein of HIV, is endowed with several biological properties in vitro, notably inhibition of the binding of both isolated gp120 and HIV-1 to the CD4 receptor, and chemotactic activity. Based on previous nuclear magnetic resonance (NMR) studies performed in our laboratory, which were consistent with a regular conformation of the C-terminal pentapeptide, and SAR studies showing that the C-terminal pentapeptide retains most of the biological properties, we designed eight hexapeptides containing in the central part either the TNYT or the TTNY sequence, and charged residues (D/E/R) at the two ends. Conformational analysis based on NMR and torsion angle dynamics showed that all peptides assume folded conformations. albeit with different geometries and stabilities. In particular, peptides carrying an acidic residue at the N-terminus and a basic residue at the C-terminus are characterized by stable helical structures and retain full chemotactic activity. The solution conformation of peptide ETNYTR displays strong structural similarity to the region 19-26 of both bovine pancreatic and bovine seminal ribonuclease, which are endowed with anti-HIV activity. Moreover, the frequent occurrence, in many viral proteins, of TNYT and TTNY, the two core sequences employed in the design of the hexapeptides studied in the present work, hints that the sequence of the C-terminal pentapeptide TTNYT is probably representative of a widespread viral recognition motif.

  • Solution structure of nocistatin, a new peptide analgesic.

    Publication Date: 01/03/2000 on Biopolymers
    by Crescenzi O, Guerrini R, Picone D, Salvadori S, Tancredi T, Temussi PA
    DOI: 10.1002/(SICI)1097-0282(200003)53:3<257::AID-BIP5>3.0.CO;2-L

    Nocistatin, a new heptadecapeptide encoded in the bPNP-3 gene, has a powerful biological activity connected with the mechanisms of pain transmission. It does not bind to the opioid receptors but to another brain receptor with high affinity. In order to substantiate these novel biological data with a structural basis, we have undertaken a conformational study in solution. Proton nmr data in helicogenic solvents are consistent with a well-defined helical structure that is consistent with the nmr parameters of the C-terminal octapeptide, a shorter fragment that retains allodynia-blocking activity.

  • Solution structure of human beta-endorphin in helicogenic solvents: an NMR study.

    Publication Date: 01/09/1999 on Journal of peptide science : an official publication of the European Peptide Society
    by Saviano G, Crescenzi O, Picone D, Temussi P, Tancredi T
    DOI: 10.1002/(SICI)1099-1387(199909)5:9<410::AID-PSC216>3.0.CO;2-R

    Beta-endorphin is the largest natural opioid peptide. The knowledge of its bioactive conformation might be very important for the indirect mapping of the active site of opioid receptors. We have studied beta-endorphin in a variety of solution conditions with the goal of testing the intrinsic tendency of its sequence to assume a regular fold. We ran NMR experiments in water, dimethylsulfoxide and aqueous mixtures of methanol, ethylene glycol, trifluoroethanol, hexafluoracetone trihydrate and dimethylsulfoxide. The solvent in which the peptide is more ordered is the hexafluoracetone trihydrate/water mixture. The helical structure detected for beta-endorphin in this mixture at 300 K extends for the greater part of its address domain, hinting at a possible mechanism of interaction with opioid receptors: a two-point attachment involving an interaction of the helical part of the address domain (PLVTLFKNAIIKNAY) with one of the transmembrane helices and a classical interaction of the message domain (YGGF) with the receptor subsite common to all opioid receptors.

  • Solution structure of dynorphin A (1-17): a NMR study in a cryoprotective solvent mixture at 278 K.

    Publication Date: 01/07/1999 on Journal of peptide science : an official publication of the European Peptide Society
    by Spadaccini R, Crescenzi O, Picone D, Tancredi T, Temussi PA
    DOI: 10.1002/(SICI)1099-1387(199907)5:7<306::AID-PSC199>3.0.CO;2-B

    Dynorphin A, the endogenous agonist for the kappa opioid receptor, has been studied by NMR spectroscopy in methanol, acetonitrile, DMSO and in mixtures of hexafluoroacetone/water and DMSO/water. NMR data in the DMSO/water cryomixture at 278 K are consistent with a conformer in which the N-terminal part, like the corresponding message domain of enkephalins, is poorly ordered, whereas the C-terminal part is folded in a loop centred around Pro10. The folded structure of the C-terminal part (address moiety) may shed light on the role of the essential residues Arg7, Lys11 and Lys13.

  • Conformational sampling of bioactive conformers: a low-temperature NMR study of 15N-Leu-enkephalin.

    Publication Date: 01/06/1998 on Journal of peptide science : an official publication of the European Peptide Society
    by Amodeo P, Naider F, Picone D, Tancredi T, Temussi PA
    DOI: 10.1002/(SICI)1099-1387(199806)4:4&lt;253::AID-PSC142&gt;3.0.CO;2-P

    Conformational studies of enkephalins are hampered by their high flexibility which leads to mixtures of quasi-isoenergetic conformers in solution and makes NOEs very difficult to detect in NMR spectra. In order to improve the quality of the NMR data, Leu-enkephalin was synthesized with 15N-labelled uniformly on all amide nitrogens and examined in a viscous solvent medium at low temperature. HMQC NOESY spectra of the labelled Leu-enkephalin in a DMSOd6/H2O) mixture at 275 K do show numerous NOEs, but these are not consistent with a single conformer and are only sufficient to describe the conformational state as a mixture of several conformers. Here a different approach to the structure-activity relationships of enkephalins is presented: it is possible to analyse the NMR data in terms of limiting canonical structures (i.e. beta- and gamma-turns) and finally to select only those consistent with the requirements of delta selective agonists and antagonists. This strategy results in the prediction of a family of conformers that may be useful in the design of new delta selective opioid peptides.

  • Design and solution structure of a partially rigid opioid antagonist lacking the basic center--models of antagonism.

    Publication Date: 01/07/1997 on European journal of biochemistry
    by Crescenzi O, Fraternali F, Picone D, Tancredi T, Balboni G, Guerrini R, Lazarus LH, Salvadori S, Temussi PA

    To discriminate between two general models of antagonism (participation and allosteric), an opioid antagonist lacking the basic nitrogen of tyramine was designed and characterized. Cyclo-[Tyr(Me)2-Tic-], the diketopiperazine of 2,6-dimethyltyrosyl-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid, is a partially rigid opioid antagonist; its pA2 (5.8) is one smaller than that of N,N-bisallyl-enkephalin but it has a very high binding affinity (10 nM) and has a delta selectivity (66 with respect to the binding to mu receptors) higher than that of naltrindole. The conformational state of this diketopiperazine, studied under a variety of solvent and temperature conditions by NMR and molecular dynamics, can be described in terms of only three conformers whose relative populations vary widely with solvent. Only one of the three conformers, characterized by a 90 degree arrangement of the aromatic rings of Tyr(Me)2 and Tic similar to those of rigid agonists and of the bioactive conformation of the corresponding linear antagonist, is consistent with the antagonist activity. This finding favors the participation model among the general mechanisms proposed to explain antagonism. Due to the simple composition of the conformational mixture and to the rigidity of the molecule, it is possible to propose a quantitative explanation for the discrepancy between the very high binding affinity (10 nM) and the fairly small in mouse vas deferens value (1.5 microM).