Search PubMed⌕ Search

Biomedical subjects

E Benedetti

Publications and source records attributed to E Benedetti.

At least 199 records · Page 11Linked to original sources
PubMed1989

Structure-toxicity relationships in the amatoxin series. Synthesis of S-deoxy[gamma(R)-hydroxy-Ile3]-amaninamide, its crystal and molecular structure and inhibitory efficiency.

The amatoxins, highly toxic components of Amanita mushrooms, strongly inhibit the DNA-dependent RNA polymerase II (or B) in eukaryotic cell nuclei. For optimal binding to the enzyme a gamma-hydroxyisoleucine side chain in the 3-position is important as in gamma-amanitin (compound 1), where the OH-group is bound in the [S]-configuration. Amanullin, a non-toxic component, having an oxygen-free isoleucine side chain no. 3, exhibits an inhibitory effect on RNA polymerase II about two orders of magnitude smaller than that of gamma-amanitin. An equal, relatively weak, inhibitory effect has previously been found with the synthetically obtained Ile3-analog 7. In the present paper the synthesis of an analog (2) bearing a gamma-hydroxyl group in the isoleucine side chain is described. The compound was found to have about the same inhibitory effect on RNA polymerase II from Drosophila embryos as amanullin and the Ile3-analog 7. Structure analysis by X-ray diffraction revealed that the hydroxyl group at the -carbon atom of side chain-3 has the [R]-configuration, the new analog thus being -deoxo[( )-hydroxy-[Ile3]-amaninamide. It follows that the [S]-configuration of this chiral center is a prerequisite to maximal toxicity. Crystallographic data demonstrating great similarity between the peptide backbones of the new analog and those of natural amatoxins are given.

Amanitins↗
PubMed1988

Long, chiral polypeptide 3(10)-helices at atomic resolution.

The crystal-state preferred conformation of the terminally blocked hepta- and octapeptides with the general formula -(Aib)n L-Leu-(Aib)2- (n = 4 and 5, respectively), determined by X-ray diffraction, was found to be a right-handed 3(10)-helix stabilized by five and six consecutive intramolecular NH...O = C H-bonds of the C(10)-III type, respectively. The octapeptide structure represents the first observation at atomic resolution of a regular, chiral 3(10)-helix larger than two complete turns. In both cases the right handed screw sense of the helix is dictated by the presence of the single, internal L-residue. This study confirms the propensity of short peptides rich in Aib, the prototype of the amino acid residues dialkylated at the alpha carbon, to adopt a 3(10)-helical structure and is expected to help our understanding of the conformational preferences of the membrane-active, channel-forming, ion-transporting peptaibol antibiotics.

Butyrates↗
PubMed1987

[A case of spasmophilic syndrome].

The case is described of a 43 year old woman with spasmophilic syndrome. For 12 years she had suffered from fainting fits, marked morning asthenia, anxiety, depression, widespread arthromyalgia, blood pressure fluctuations, precordial pains, paresthesia and painful nocturnal cramp. This clinical picture appeared in a subject with a double left kidney and stones in the supernumerary ureter, enlargement of the pancreatic head and tail revealed by a CAT scan and an earlier cholecystectomy. Given the multiplicity of symptoms diagnosis was necessarily by a process of elimination. The data providing grounds for optimism were a positive Chvostek's sign, stable calcium phosphorus profiles, a reduction in ionised calcium and favourable eletromyographic readings.

Adult↗
PubMed1987

[A case of amyloidosis associated with a solitary micromolecular plasmocytoma].

Amyloidosis associated with myeloma and its current classification are examined. The clinical example is reported of a patient with isolated micromolecular plasmocytoma in whom the amyloidosis appeared during the remission of the primary disease. The patient was not seen until a late stage when he was admitted to hospital with severe cardiac decompensation. Echocardiography revealed the location to be the cardiac muscle. The increase in left ventricular mass revealed by the ECG was in contrast with the low ECG voltages. Biopsy showed involvement of the oral cavity. The condition resisted all treatment and the patient died a few months after the onset of the amyloidosis. The view that amyloidosis associated with plasma cell dyscrasias should be classified with primary amyloidosis is supported.

Amyloidosis↗
PubMed1987

Autoantibodies in 16 patients with extensive burns and a review of the literature.

Serum samples were taken during the first 3 weeks and 1 year after discharge from hospital of 16 patients with burns covering more than 35 per cent of the body surface area. The sera were tested for the presence of antinuclear, antimitochondrial, anti smooth muscle, anti brush border and anti gastric parietal cell autoantibodies using the technique of indirect immunofluorescence. Compared with measurements for the same autoantibodies, in sera from 25 healthy blood donors, the burned patients' sera showed the presence of anti smooth muscle autoantibodies in 81.2 per cent, anti brush border autoantibodies in 56.2 per cent, antimitochondrial autoantibodies in 31.2 per cent and antinuclear autoantibodies in 12.5 per cent of the sera. Autoantibodies to gastric parietal cells were not detected. A correlation was noted between the presence of antimitochondrial autoantibodies and alterations in liver function. In contrast, no correlations were found between the raised levels of the various autoantibodies and resuscitative fluid or antibiotic therapy, intercurrent infections, serum immunoglobulin levels, surgical treatment or the duration of stay in hospital. The high titre of autoantibodies to anti smooth muscle could have arisen from tissue protein degradation associated with the raised requirements for energy by the hypermetabolic patients.

Adult↗
PubMed1986

Long polypeptide 3(10)-helices at atomic resolution.

The crystal-state preferred conformation of the terminally blocked homooctapeptide from the C(alpha,alpha)-dimethylated alpha-aminoisobutyric acid (Aib) residue, pBrBz-(Aib)(8)-OBu(t), in which pBrBz is para-bromobenzoyl and OBu(t) is tert-butoxy, determined by x-ray diffraction analysis using direct methods, was found to be a 3(10)-helix stabilized by six consecutive intramolecular N-H....O=C hydrogen bonds of the C(10)-III (or III') type. This is the first observation at atomic resolution of a regular 3(10)-helix longer than two complete turns. The solid-state structural analysis was extended to the terminally blocked, alpha-aminoisobutyric acid-rich octapeptide corresponding to the 2-9 sequence of the peptaibol antibiotics emerimicins III and IV, pBrBz-Aib(3)-L-Val-Gly-L-Leu-Aib(2)-OMe. Again, this peptide adopts a (right-handed) 3(10)-helical structure, although slightly distorted at the level of the L-leucine residue. The role of specific amino acid sequence and peptide main-chain length in stabilizing either the 3(10)- or the alpha-helical conformation and their possible implications on the nature of the channel formed by peptaibol antibiotics in the membrane are also briefly discussed.

Journal Article↗
PubMed1985

New possibilities of research in chronic lymphatic leukemia by means of Fourier transform-infrared spectroscopy--II.

Ten samples of lymphocytes coming from patients affected by chronic lymphatic leukemia and ten samples from normal subjects were studied by FT-IR spectroscopy. Spectral differences observed between the two kinds of cells correspond to an increase of the intensities, in the leukemic samples with respect to the normal ones, of the bands corresponding mainly to PO2- symmetrical and asymmetrical stretching vibrations of DNA. The ratios of the integrated areas of the band at 1080 cm-1 mainly involving the symmetrical stretching vibration of the O-P-O linkages of DNA, and of the band at 1540 cm-1, due to the proteic components of the lymphocytes, assume different values for the two kinds of cells. These ratios can constitute an additional marker to diagnose chronic lymphatic leukemia and may be usefully employed to evidence the early phases of the disease.

Chronic Disease↗
PubMed1985

Molecular structure of peptaibol antibiotics: solution conformation and crystal structure of the octapeptide corresponding to the 2-9 sequence of emerimicins III and IV.

The infrared absorption and 1H nuclear magnetic resonance analyses of chloroform solutions of the terminally-blocked segment corresponding to the 2-9 sequence of emerimicins III and IV, -(Aib)3-L-Val-Gly-L-Leu-(Aib)2-, are consistent with the presence of a 3(10)-helical structure of high thermal stability. The crystal structure of the octapeptide, obtained by X-ray diffraction indicates the formation of a right-handed 3(10)-helix, stabilized by six consecutive intramolecular N-H....O:C H-bonds, slightly distorted at the level of the L-Leu residue.

Amino Acid Sequence↗
PubMed1984

Analytical infrared spectral differences between human normal and leukaemic cells (CLL)--I.

Two series of normal and leukaemic lymphocytes were examined by infrared spectroscopy in order to try to find spectral differences connected with chemical and biological modifications. The bands at 965 and 530 cm-1 present only in the spectra of leukaemic lymphocytes, assume particular significance. The C-H stretching region furnishes useful indications about the different ratios of the methyl groups compared with the methylene ones in the two cases. The infrared bands characteristic of the leukaemic lymphocytes seem to be due to chemical modifications not involving the DNA chain.

Humans↗
PubMed1984

Modified calmodulin calcium binding domain III. Solid phase synthesis, purification and 1H n.m.r. characterization.

The dodecapeptide Ac-Asp-Lys-Asp-Gly-Asn-Gly-Tyr-Ile-Ser-Ala-Ala-Gaba-OH is a modified calmodulin calcium binding domain III. The synthesis of the peptide by the solid phase method with a total protection scheme using PAM-resin is reported. The purified compound has been characterized by 1H n.m.r. spectroscopy, both in the presence and in the absence of calcium ions, at various pHs. No strong specific interaction seems to occur between the peptide and Ca++ ions in water solutions.

Binding Sites↗
PubMed1983

Structure of N-tert-butyloxycarbonyl-D-leucyl-L-phenylalanylethanolamide. An N alpha-protected analogue of the COOH-terminal dipeptide of linear gramicidins.

Solid state conformational analysis of N-tert-butyloxycarbonyl-D-leucyl-L-phenylalanylethanolamide (t-Boc-D-Leu-L-Phe-EA), an N alpha-protected analogue of the COOH-terminal dipeptide of linear gramicidins, carried out by x-ray diffraction, has indicated that the molecules are characterized by an N-H...O = C intramolecularly hydrogen-bonded chain reversal of the beta-turn II' type. One of the two independent molecules in the asymmetric unit shows an additional intramolecular hydrogen bond of the O-H...O = C type, linking the hydroxyl function of the COOH-terminal ethanolamide moiety to the carbonyl oxygen of the urethane N-protecting group. This is the first experimental evidence for a beta-turn conformation fused with the oxy analogue of an alpha-turn. The results of an investigation in a solvent of low polarity (deuteriochloroform), using infrared absorption and 1' nuclear magnetic resonance, strongly support the view that an intramolecularly hydrogen-bonded beta-turn conformation is the most populated conformation of t-Boc-D-Leu-L-Phe-EA molecules at high dilution. In the self-association process, taking place at high concentration, the urethane and peptide NH groups are involved as hydrogen-bonding donors.

Amino Acid Sequence↗
PubMed1983

First observation of a beta-turn conformation fused with the oxy-analogue of an alpha-turn: the molecular structure of a model peptide of the C-terminal part of gramicidin A.

The molecular structure of N-tert-butyloxycarbonyl-D-leucyl-L-phenylalanyl ethanolamide (t-Boc-D-Leu-L-Phe-EA), a protected analogue of the C-terminal dipeptide of the membrane-active linear antibiotic gramicidin A, has been determined by X-ray diffraction. One of the two independent molecules in the asymmetric unit is characterized by a chain reversal stabilized by an intramolecular, three-centre, double hydrogen bonding. It represents the first experimental evidence for a beta-turn conformation fused with the oxy-analogue of an alpha-turn.

Chemical Phenomena↗
PubMed1983

Statistical and energetic analysis of side-chain conformations in oligopeptides.

The distributions of side-chain conformations in 258 crystal structures of oligopeptides have been analyzed. The sample contains 321 residues having side chains that extend beyond the C beta atom. Statistically observed preferences of side-chain dihedral angles are summarized and correlated with stereochemical and energetic constraints. The distributions are compared with observed distributions in proteins of known X-ray structures and with computed minimum-energy conformations of amino acid derivatives. The distributions are similar in all three sets of data, and they appear to be governed primarily by intraresidue interactions. In side chains with no beta-branching, the most important interactions that determine chi 1 are those between the C gamma H2 group and atoms of the neighboring peptide groups. As a result, the g- conformation (chi 1 congruent to -60 degrees) occurs most frequently for rotation around the C alpha-C beta bond in oligopeptides, followed by the t conformation (chi 1 congruent to 180 degrees), while the g+ conformation (chi 1 congruent to 60 degrees) is least favored. In residues with beta-branching, steric repulsions between the C gamma H2 or C gamma H3 groups and backbone atoms govern the distribution of chi 1. The extended (t) conformation is highly favored for rotation around the C beta-C gamma and C gamma-C delta bonds in unbranched side chains, because the t conformer has a lower energy than the g+ and g- conformers in hydrocarbon chains. This study of the observed side-chain conformations has led to a refinement of one of the energy parameters used in empirical conformational energy computations.

Amino Acids↗
PubMed1983

Protected 1-3 segment of the peptaibol antibiotics alamethicin and hypelcin. Solid-state and solution study of a stereochemically constrained linear peptide.

A study of the modes of folding and self-association of Z-Aib-L-Pro-Aib-OMe (the protected 1-3 segment of the peptaibol antibiotics alamethicin and hypelcin) in the solid state was performed using i.r. absorption and X-ray diffraction. The stereochemically constrained tripeptide molecules adopt a 4 leads to 1 intramolecularly H-bonded form (beta-turn), where the single intramolecular H-bond is found between the peptide N-H group of the Aib3 residue and the urethane C = O group of the N-blocking benzyloxycarbonyl moiety. This folded structure is stabilized by an intermolecular H-bond between the urethane N-H group of the Aib1 residue and the peptide C = O group of the Pro2 residue of a symmetry related molecule. According to the i.r. absorption data, in CH2Cl2 and TMP solutions the same intramolecularly H-bonded form occurs as that found in solid state. Compared to the situation in the solid state, in CH2Cl2 and TMP solvation of the urethane N-H group replaces self-association (through the same N-H group). The results are also discussed in relation to those obtained for other protected -Aib-X-Aib- (X = Aib, L-Ala, L-Val) tripeptide segments of peptaibol antibiotics.

Alamethicin↗
PubMed1983

Bioorganic stereochemistry. A study of the peptide oxazolones from Z-(Aib)n-OH (n = 2-4) in the solid state.

An investigation of the preferred conformations and modes of self-association of the peptide oxazolones from Z(-Aib-)n-OH (n = 2-4) in the solid state has been performed by infrared absorption. More detailed information on the peptide oxazolone from Z(-Aib-)3OH(2) has been obtained using X-ray diffraction. In this compound the conformations of the first two Aib residues differ substantially, only the N-terminal one being found in the usual 3(10)-(or alpha-) helical region of the Ramachandran map. The C = N-bond of the oxazolone group is not conjugated with the lactone moiety. A very weak intermolecular interaction occurs between the urethane N-H and the carbonyl group of the oxazolone ring.

Aminoisobutyric Acids↗
PubMed1983

Preferred conformation of the benzyloxycarbonyl-amino group in peptides.

Structural parameters, derived from X-ray crystallographic data, have been compiled for 35 derivatives of amino acids, peptides, and related compounds, which contain the N-terminal benzyloxycarbonyl (Z) group. The geometry of the urethane moiety of this end group is closely similar to that of the tert-butoxycarbonyl (Boc) group, except for a relaxation of some bond angles because the Z group is sterically less crowded than the Boc group. For the same reason, the Z group has greater conformational flexibility. As a result, packing forces in the crystal may cause greater deformations of bond angles, resulting in larger variations of observed bond lengths and bond angles than in Boc-peptide crystals. The aromatic rings of the Z end groups tend to stack in crystals. Conformational energy calculations indicate that most conformations of Z-amino acid-N'-methylamides and of corresponding Boc derivatives have similar dihedral angles and relative energies, i.e. the nature of the N-terminal end group has little effect on the conformational preferences of the residue next to it. In particular, the computed fraction of molecules with a cis urethane (C-N) bond is similar for the two derivatives: 0.51 and 0.42 in Boc-Pro-NHCH3 and Z-Pro-NHCH3, respectively, and 0.02 in the two Ala derivatives. There exist several computed conformations of Z-Ala-NHCH3 and Z-Pro-NHCH3 in which the phenyl ring and the C-terminal methylamide group are close to each other. Because of favorable nonbonded interactions, such conformations are of low energy.

Amino Acids↗