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 conformation of nociceptin.

    Publication Date: 28/04/1997 on Biochemical and biophysical research communications
    by Salvadori S, Picone D, Tancredi T, Guerrini R, Spadaccini R, Lazarus LH, Regoli D, Temussi PA
    DOI: 10.1006/bbrc.1997.6285

    Nociceptin, a novel heptadecapeptide, interacts with ORL1 a G protein-coupled receptor whose sequence is closely related to that of the kappa opioid receptor but has no opioid activity. We have investigated the conformational preferences of Nociceptin also in comparison to Dynorphin A. The N-terminal part of Nociceptin has the same conformational preferences of the message of endogenous opioids but the C-terminal part of the sequence is more flexible than the corresponding address of Dynorphin A. [Tyr1]-Nociceptin, while retaining nociceptive activity, has also an opioid activity comparable to that of enkephalins.

  • Delta-selective opioid peptides containing a single aromatic residue in the message domain: an NMR conformational analysis.

    Publication Date: 01/09/1996 on Journal of peptide science : an official publication of the European Peptide Society
    by Crescenzi O, Amodeo P, Cavicchioni G, Guerrini R, Picone D, Salvadori S, Tancredi T, Temussi PA
    DOI: 10.1002/psc.56

    The sequence of deltorphin I, a delta-selective opioid agonist, has been systematically modified by inserting conformationally constrained C alpha, alpha disubstituted apolar residues in the third position. As expected, substitution of Phe with Ac6c, Ac5c and Ac3c yields analogues with decreasing but sizeable affinity. Surprisingly, substitution with Aib yields an analogue with almost the same binding affinity of the parent compound but with a greatly increased selectivity. This is the first case of a potent and very selective opioid peptide containing a single aromatic residue in the message domain, that is, only Tyr1. Here we report a detailed conformational analysis of [Aib3]deltorphin I and [Ac6c3]deltorphin I in DMSO at room temperature and in a DMSO/water cryomixture at low temperature, based on NMR spectroscopy and energy calculations. The peptides are highly structured in both solvents, as indicated by the exceptional finding of a nearly zero temperature coefficient of Val5 NH resonance. NMR data cannot be explained on the basis of a single structure but it was possible to interpret all NMR data on the basis of a few structural families. The conformational averaging was analysed by means of an original computer program that yields qualitative and quantitative composition of the mixture. Comparison of the preferred solution conformation with two rigid delta-selective agonists shows that the shapes of [Aib3]deltorphin I and [Ac6c3]deltorphin I are consistent with those of rigid agonists and that the message domain of opioid peptides can be defined only in conformational terms.

  • 3(10)-Helices, helix screw sense and screw sense reversal in the dehydro-peptide Boc-Val-delta Phe-Gly-delta Phe-Val-OMe.

    Publication Date: 01/01/1996 on Journal of peptide science : an official publication of the European Peptide Society
    by Tuzi A, Ciajolo MR, Picone D, Crescenzi O, Temussi PA, Fissi A, Pieroni O
    DOI: 10.1002/psc.47

    The pentapeptide Boc-Val-delta Phe-Gly-delta Phe-Val-OME, containing two dehydro-phenylalanine (delta Phe) residues, has been synthesized and its structure investigated. In the crystalline state, the molecule adopts a right-handed 3(10)-helical conformation stabilized by two intramolecular hydrogen bonds between CO of Val1 and NH of delta Phe4, and between CO of delta Phe2 and NH of Val5, respectively. NMR measurements are consistent with the presence of 3(10)-helical structures also in acetonitrile and dimethylsulphoxide solution: the distances between backbone protons estimated from NOE connectivities are in overall agreement with those observed in the solid state; the chemical shifts of the amide protons show the smaller temperature coefficients for the NHs that in solid state are involved in intramolecular hydrogen bonds. The CD spectra in acetonitrile, chloroform, methanol and dimethylsulphoxide display exciton couplets of bands corresponding to the delta Phe electronic transition at 280 nm; the sign of the bands is consistent with the presence of helical structures having a prevalent left-handed screw sense. Addition of 1,1,1,3,3,3-hexafluoro-propan-2-ol gives rise to the gradual appearance of a couplet of opposite sign, suggesting the helix reversal from left-handed sense to right-handed sense. The conformational behaviour is discussed on the basis of the specific sequence of the peptide.

  • Conformational analysis of potent and very selective delta opioid dipeptide antagonists.

    Publication Date: 27/12/1995 on FEBS letters
    by Amodeo P, Balboni G, Crescenzi O, Guerrini R, Picone D, Salvadori S, Tancredi T, Temussi PA
    DOI: 10.1016/0014-5793(95)01374-1

    The delta selectivity and antagonism of peptides containing L-tetrahydro-3-isoquinoline carboxylic acid (Tic) in second position can be attributed mainly to the Tyr-Tic unit. These properties can be further enhanced by substituting Tyr1 with 2,6-dimethyl-L-tyrosyl (Dmt). Dmt-Tic-NH2, Dmt-Tic-OH, Dmt-Tic-Ala-NH2 and Dmt-Tic-Ala-OH are all more active and/or selective than the corresponding [Tyr1]-parent peptides. In fact the selectivities of Dmt-Tic-OH and Dmt-Tic-Ala-OH are the highest ever recorded for opioid molecules. 1H NMR spectra in a DMSO/water mixture at 278 K reveal the presence of two similar conformers, characterised by a cis or trans Dmt-Tic bond, in all four peptides. A detailed conformational analysis in solution of Dmt-Tic-NH2 shows that these conformers have a shape very similar to that of the bioactive conformation of Tyr-Tic-NH2 and to that of naltrindole.

  • Delta opioidmimetic antagonists: prototypes for designing a new generation of ultraselective opioid peptides.

    Publication Date: 01/09/1995 on Molecular medicine (Cambridge, Mass.)
    by Salvadori S, Attila M, Balboni G, Bianchi C, Bryant SD, Crescenzi O, Guerrini R, Picone D, Tancredi T, Temussi PA

    Tyr-Tic (1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid) and Tyr-Tic-Ala were the first peptides with delta opioid antagonist activity lacking Phe, considered essential for opioid activity based on the N-terminal tripeptide sequence (Tyr-D-Xaa-Phe) of amphibian skin opioids. Analogs were then designed to restrain the rotational flexibility of Tyr by the substitution of 2,6-dimethyl-L-tyrosine (Dmt).

  • Solution and solid-state structure of the diketopiperazine of tyrosyl-tetrahydroisoquinoline-3-carboxylic acid.

    Publication Date: 01/08/1995 on International journal of peptide and protein research
    by Ciajolo MR, Balboni G, Picone D, Salvadori S, Tancredi T, Temussi PA, Tuzi A

    delta-Selective antagonism of [L-Tic2]-peptides, including the simple dipeptide Tyr-L-Tic-NH2, is linked to the Tyr-Tic-"recognition site". In order to gain further information on the conformational preferences of the Tyr-Tic-moiety we have undertaken a structural study of a cyclic analog, the diketopiperazine of Tyr-Tic. A conformational study of cyclo[-Tyr-Tic-], that is almost devoid of opioid activity, can also be useful to discriminate between the role of the two aromatic rings and of the basic nitrogen in determining antagonism. The structure of cyclo[-Tyr-Tic-] has been solved in a DMSO/water solution at 278 K by NMR spectroscopy and in the solid state by X-ray diffraction methods. The two informations are almost identical, with an arrangement of the aromatic rings rather different from that of the putative bioactive conformation of the parent linear dipeptide. This difference points to the importance of conformational effects and is in agreement with the hypothesis that the positive center may be not essential for antagonism.

  • Assignment and secondary-structure determination of monomeric bovine seminal ribonuclease employing computer-assisted evaluation of homonuclear three-dimensional 1H-NMR spectra.

    Publication Date: 15/04/1995 on European journal of biochemistry
    by D'Ursi A, Oschkinat H, Cieslar C, Picone D, D'Alessio G, Amodeo P, Temussi PA

    Monomeric bovine seminal ribonuclease (mBS-RNase), the subunit of dimeric bovine seminal ribonuclease (BS-RNase), is an unusual monomer: for its structural stability, its catalytic activity, which is even higher than that of the parent dimeric enzyme, and for its role as an intermediate in the refolding of dimeric BS-RNase. Here we present the proton NMR assignment and secondary-structure determination of mBS-RNase, with a comparison of its structure to the structure of its parent protein, and to the structure of RNase A, a homologue with more than 80% identity in amino acid sequence. Proton NMR assignment was performed using a computer-assisted procedure, through a partially automated analysis of homonuclear three-dimensional spectra [Oschkinat, H., Holak, T. A. & Cieslar, C. (1991) Biopolymers 31, 699-712]. The secondary structures of mBS-RNase, of the A chain of dimeric BS-RNase, and of RNase A, are found to be similar. Significant differences are found instead, between mBS-RNase and RNase A in the more flexible stretches of the molecule, where a higher number of substitutions is present. Furthermore, a preliminary tertiary-structure model is reported, showing that the overall folding of mBS-RNase is closer to that of RNase A rather than that of (dimeric) BS-RNase.

  • Conversion of enkephalin and dermorphin into delta-selective opioid antagonists by single-residue substitution.

    Publication Date: 15/08/1994 on European journal of biochemistry
    by Tancredi T, Salvadori S, Amodeo P, Picone D, Lazarus LH, Bryant SD, Guerrini R, Marzola G, Temussi PA

    The properties of di- and tri-peptides containing 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (Tic) in second position suggest that the message domain of opioid peptides can be composed of only two residues [Temussi, P. A., Salvadori, S., Amodeo, P., Guerrini, R., Tomatis, R., Lazarus, L. H., Picone, D. & Tancredi, T. (1994) Biochem. Biophys. Res. Commun. 198, 933-939]. As a crucial test of the possibility that the Tyr-Tic segment be a message domain in longer peptide sequences, we have inserted it in the sequences of two typical opioid peptides: [Leu]enkephalin, a non-selective agonist, and dermorphin, a selective mu agonist. Here we report the synthesis and biological activity of [L-Tic2]enkephalin, [L-Tic2]dermorphin, [L-Tic2]dermorphin carboxylic acid and [D-Tic2]dermorphin: all [L-Tic2]peptides were converted from agonists to delta-selective antagonists. The NMR conformational study in a dimethylsulfoxide/water cryoprotective mixture at low temperature shows diagnostic side-chain--side-chain NOEs in the spectra of all [L-Tic2]peptides and hints that the 90 degrees arrangement of the the two aromatic rings found in the cis-Tyr-L-Tic moiety, typical of N-methyl naltrindole and other delta-selective opiate antagonists, is responsible for the antagonist activity of all these peptides.

  • Selective opioid dipeptides.

    Publication Date: 15/02/1994 on Biochemical and biophysical research communications
    by Temussi PA, Salvadori S, Amodeo P, Bianchi C, Guerrini R, Tomatis R, Lazarus LH, Picone D, Tancredi T
    DOI: 10.1006/bbrc.1994.1133

    The surprising change of selectivity induced by the change of chirality in peptides containing the tetrahydro-3-isoquinoline carboxylic acid (Tic) in second position, interpreted as a conformational preference induced on the Tyr-Xaa-Phe domain, can instead be attributed to the Tyr-Tic message domain. The relative spatial disposition of the aromatic ring of delta-selective non peptidic opiates is compatible with a message domain, in opioid peptides, of only two residues. This hypothesis was tested through the synthesis of Tyr-L-Tic-NH2, Tyr-D-Tic-NH2, Tyr-L-Tic-Ala-NH2, Tyr-L-Tic-Ala-OH and Tyr-D-Tic-Ala-NH2. Peptides containing Tyr-L-Tic- behave as very selective delta antagonists and those containing Tyr-DTic- as non selective agonists. This is the first case of opioid peptides containing a two-residue message domain and of opioid dipeptides with substantial opioid activity.

  • Solution structure of casokefamide.

    Publication Date: 31/03/1993 on Biochemical and biophysical research communications
    by Brantl V, Picone D, Amodeo P, Temussi PA
    DOI: 10.1006/bbrc.1993.1295

    Casokefamide (Tyr-D-Ala-Phe-D-Ala-Tyr-NH2) is a synthetic peptide derived from the beta-casomorphin sequence, designed to increase the resistance to gastric proteases. Casokefamide binds to both mu and delta-opioid receptors, while beta-casomorphins and its fragments are typical mu-opioid receptor agonists. Furthermore, casokefamide can affect gastric acid and pancreatic exocrine secretions and also gastrointestinal motility. We have undertaken a conformational study on this peptide based on NMR measurements in a DMSOd6/H2O cryomixture at 265 K and energy calculations. The predominant conformation is characterised by the absence of regular structures and intramolecular hydrogen bonds. The conformation of the message domain is reminiscent of the shape of several peptidic and non peptidic opiates, with the D-Ala2CH3 group sandwiched between Tyr1 and Phe3 aromatic rings.