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T Tancredi

Publications and source records attributed to T Tancredi.

At least 55 records · Page 3Linked to original sources
PubMed1989

Ala analogues of the cyclolinopeptide A.

Analogues of cyclolinopeptide A, due to the replacement of each amino acid in the Pro1-Pro2-Phe3-Phe4 sequences with an L-Ala residue, were synthesized by classical method in solution. Mixed anhydride and N,N'-dicyclohexylcarbodiimide coupling methods have been used for the synthesis of both linear and cyclic peptides. The products were characterized by Rf values and uv spectra, as well as by fast atom bombardment spectroscopy. 1H-nmr studies on [Ala2] analogues are also reported. Preliminary data in CDCl3 solution, at low temperature, seems more promising.

Alanine↗
PubMed1989

Comparison of the conformations of cyclolinopeptide A in the solid state and in solution.

Cyclolinopeptide A, a cyclic nonapeptide isolated from linseed, has lately attracted large interest for its cytoprotective activity. The recent elucidation of its solid state structure has prompted us to undertake a detailed conformational analysis in solution. Room-temperature 1H-nmr spectra in several solvents (DMSO-d6, DMSO-d6/D2O/H2O, CD3OH, (CD3)2CDOH, CDCl3) all show very broad lines, indicating the presence of chemical exchange among several conformers. It proved possible to freeze a single conformational state in CDCl3 at 214 K. Unusual chemical shifts and nuclear Overhauser enhancements are consistent with the main features of the solid state structure.

Peptides, Cyclic↗
PubMed1987

Experimental attempt to simulate receptor site environment. A 500-MHz 1H nuclear magnetic resonance study of enkephalin amides.

The amides of Leu5-enkephalin, Met5-enkephalin, and three analogues, D-Ala2,Leu5-enkephalin, (AcO)Tyr1,Met5-enkephalin, and (AcO)Tyr1,D-Ala2,Met5-enkephalin, have been studied by means of 1H NMR spectroscopy in two different solvent systems: Me2SO-d6 and CDCl3. In the latter solvent the peptides were dissolved as complexes with 18-crown-6-ether, a coronand that binds strongly to the NH3+ groups. The crown ether complexation and the apolar solvent were used to simulate the anionic subsite of the receptor and the hydrophobic environment of the receptor cavity, respectively. The very unusual amide proton chemical shifts and their temperature coefficients suggest the presence of folded conformations in CDCl3 for all peptides, consistent with several models of opioid receptors and with the crystal structure of Leu5-enkephalin. The differences among the proposed cyclic conformations of the five peptides may be correlated, in part, with their different biological activity. All peptides in Me2SO-d6 are characterized by complex mixtures of extended fully solvated conformations.

Enkephalin, Leucine↗
PubMed1987

Nuclear Overhauser effects in linear peptides. A low-temperature 500 MHz study of Met-enkephalin.

Met5-enkephalin was studied in 1 mM solutions in 2H2O at room temperature and in a cryoprotective mixture (DMSOd6/2H2O, mole fraction of DMSO 0.49) in the temperature range 265-298 K. Small positive effects were observed between the ortho and meta protons of Tyr in aqueous solution at room temperature. Intraresidue effects can be made strong and negative by increasing the viscosity of the medium with a combination of cryoprotective mixtures and low temperatures. The use of mixtures with properties very close to water is very promising for conformational studies of enkephalins and of other small linear peptides.

Cold Temperature↗
PubMed1987

A 500-MHz proton nuclear magnetic resonance study of mu opioid peptides in a simulated receptor environment.

The structure-activity relationship of several mu selective opioid peptides has been evaluated on the basis of both experimental and theoretical approaches. The conformations of Tyr-D-Ala-Phe-Gly-NH2, the tetrapeptide N-fragment of dermorphin, and two analogues have been studied in solution by 1H NMR spectroscopy. The physicochemical environment inside the receptor has been simulated by complexing the peptides with a crown ether and dissolving the complexes in chloroform. The family of conformations derived from the NMR data possesses most of the features previously proposed for mu agonists and is fully consistent with an original model of the mu receptor based on the structures of many rigid opiates. As a simple test of this model, the synthesis of a linear peptide with significant mu activity in spite of the absence of Tyr1 is reported.

Animals↗
PubMed1984

Experimental simulation of the environment of the delta opioid receptor. A 500 MHz study of enkephalins in CDCl3.

Complexes of [Met5] and [Leu5]enkephalin amides with 18-crown-6-ether have been studied in CDCl3 solution by means of 500 MHz NMR spectroscopy, in order to simulate two of the features of the opioid receptor: the apolar environment and the binding of the charged N atom. Contrary to all previous studies in polar solvents the NH resonances are spread in a huge range (ca. 4 ppm) as in the spectra of rigid cyclic peptides. The two observed intramolecular hydrogen bonds are consistent with the existence of a single, folded, conformation, i.e. a C10 beta-turn in which the Phe4 NH is linked to the Tyr1 CO group.

Chemical Phenomena↗
PubMed1984

Interaction between domains in chromosomal protein HMG-1.

Peptides corresponding to the N-terminal, central and central plus C-terminal domains of high mobility group protein HMG-1 from calf thymus have been isolated after digestion in solution with protease V8 under structuring conditions (0.35 M NaCl, pH 7.1). The effect of the interaction of these peptides with DNA on the topological properties of the nucleic acid has been studied and compared with the change in superhelicity produced by the whole protein. It appears that the region responsible for this effect is the central domain of HMG-1. The isolated N-terminal and central domains of this protein maintain their secondary and tertiary structure as observed by spectroscopic techniques. However, when the central domain is covalently linked only to the acidic C-terminal part of the molecule, its secondary and tertiary structures are lost as well as its property to alter DNA superhelicity. The results are discussed in relation to the interactions occurring between the different domains and the possible functional interactions of this protein.

Amino Acids↗
PubMed1983

Interaction of conformationally flexible agonists with the active site of sweet taste. A study of arylureas.

The conformation of tolylureas has been studied by means of X-ray diffraction, NMR spectroscopy, and semiempirical quantum-mechanical calculations. The flat shape of meta and para isomers allows a good interaction with the model sites for bitter and sweet taste, respectively, whereas the ortho isomer cannot fit the sites because of the relative arrangements of the aryl and amide planes and because of poor hydrophobic interactions. The consistency of the conformational results with the sweet taste model site, previously proposed by the authors, is emphasized by the good fit of dulcine, a sweeter para-substituted arylurea.

Humans↗
PubMed1982

Interaction of oxidized and reduced uteroglobin with progesterone.

Binding of added progesterone to native uteroglobin requires the reduction of the disulfide bonds that hold together the two polypeptide chains of the protein. The hypothesis that in the native oxidized state of uteroglobin the steroid binding cavity is preformed and occupied by a progesterone molecule has been tested by several experimental means. The results demonstrate that progesterone does not interact with oxidized uteroglobin, and show that the majority of the oxidized uteroglobin molecules purified from pseudopregnant rabbits do not contain a progesterone molecule. Oxidation of reduced uteroglobin in the presence of saturating amounts of progesterone does not result in significant retention of the steroid inside the oxidized protein.

Amino Acid Sequence↗
PubMed1980

Interaction of S-carboxymethylated uteroglobin with progesterone.

S-Carboxymethylated uteroglobin, a small progesterone-binding globular protein, was studied by means of high-field proton magnetic resonance spectroscopy. Conformational changes induced by the steroid have been observed and indicate a well-defined rearrangement of the structure of the protein. The unusual stoichiometry of one progesterone to two uteroglobin dimers is confirmed by 1H NMR. His-8 plays a central role in the mechanism of interaction of uteroglobin with progesterone. The pH dependence of affinity constant for the complexation of the steroid parallels the titration of this histidine. Although it is not a part of the active site, it influences a crucial conformational transition of the protein through the charge carried by its imidazole ring. Formation of a tetramer of uteroglobin subunits able to bind progesterone is critically compared to a kinetic scheme involving only dimers.

Animals↗
PubMed1980

Interaction of alpha-L-aspartyl-D-phenylalanine methyl ester with the receptor site of the bitter taste.

The analysis of the structure-activity relationship previously performed on the sweet L,L isomer of Asp-Phe-OMe was extended to the bitter L,D diastereoisomer. A combination of NMR measurements and of an original method of PEM calculations gives a description of the conformational state of the L,D isomer that can be effectively used to study the interaction with a previously proposed model of the bitter taste receptor site.

Aspartame↗
PubMed1979

Carbon magnetic resonance studies of the self-aggregation of calf thymus histones.

Self-aggregation of calf thymus histones H2A and H4 was studied by means of 13C magnetic resonance. Analyses of the changes in the intensities of several side-chain resonances, induced by added NaCl, confirm that carbon magnetic resonance can be used to monitor aggregation phenomena more accurately than other physicochemical methods. In particular the validity of an original computer-based method to treat 13C intensities is confirmed. The details of these aggregation phenomena are critically discussed in the light of a simple experiment on a 13C-enriched sample of H2B.

Animals↗
PubMed1978

Three-dimensional mapping of the sweet taste receptor site.

The active sites of the receptors for sweet and bitter tastants are shown to be related by a simple symmetry operation. This relationship, in turn, allows the identification of the critical geometrical features of both receptor sites. The model proposed for the sweet site is shown to be consistent with a large number of (conformationally rigid) sweet molecules.

Models, Molecular↗
PubMed1976

A study of calf-thymus histone H2B using 13C magnetic resonance.

Calf thymus histone H2B has been studied by means of 13c magnetic resonance. Most sidechain resonances have been assigned. Analysis of 13c peak intensities by a simple computer-aided method proves that 13c magnetic resonance spectroscopy can be used to monitor aggregation phenomena more accurately than 1H magnetic resonance or other physico-chemical methods. Re-examination of 1H spectral simulations shows substantial agreement with 13C results. It is concluded that in 0.1M added NaCL the H2b aggregates include the chain segment from 50 (+/-5) to 108 (+/-5).

Animals↗