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B Di Blasio

Publications and source records attributed to B Di Blasio.

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

Regularly alternating L,D-peptides. III. Hexacyclic peptides from valine or phenylalanine.

In the present paper we describe the single-crystal x-ray analyses of two cyclic hexapeptides containing an equal number of alternating L,D-residues as putative analogues of the metal binding compounds, enniatin and beauvericine. Both the molecules of c(L-Val-D-Val)3 and C(L-Phe-D-Phe)3 retain in the solid state the center of symmetry and crystallize with six and eight trifluoroacetic acid molecules, respectively. The peptides are strongly hydrogen bonded to the solvent molecules. We estimate, on the basis of the molecular geometry and spatial arrangement of the peptide carbonyl groups and in comparison with other metal binding cyclic peptides, the ability of these molecules to interact with metal ions as 1:1 complexes.

Isomerism↗
PubMed1989

Structural versatility of peptides containing C alpha, alpha-dialkylated glycines: conformational energy computations, i.r. absorption and 1H n.m.r. analysis of 1-aminocyclopropane-1-carboxylic acid homopeptides.

Conformational energy computations on the 1-aminocyclopropane-1-carboxylic acid mono-, di-, and tripeptide amides, Ac-(Ac3c)n-NHMe (n = 1-3), indicate that this C alpha, alpha-dialkylated, cyclic alpha-amino acid residue is conformally restricted and that type-I(I') beta-bends and distorted 3(10)-helices are particularly stable conformations for the di- and tripeptide amides, respectively. The results of the theoretical analysis are in agreement with those obtained in an i.r. absorption and 1H n.m.r. investigation in chloroform solution of Ac3c-rich tri- and tetrapeptide esters. A comparison is also made with the conclusions extracted from our previous work on peptides rich in Aib (alpha-aminoisobutyric acid), Ac5c (1-aminocyclopentane-1-carboxylic acid), and Ac6c (1-aminocyclohexane-1-carboxylic acid).

Alkylation↗
PubMed1989

Structural versatility of peptides containing C alpha, alpha-dialkylated glycines. An X-ray diffraction study of six 1-aminocyclopropane-1-carboxylic acid rich peptides.

The molecular and crystal structures of six fully blocked, Ac3c-rich peptides to the tetramer level were determined by X-ray diffraction. The peptides are Fmoc-(Ac3c)2-OMe-CH3OH, Ac-(Ac3c)2-OMe, t-Boc-Ac3c-L-Phe-OMe, pBrBz-(Ac3c)3-OMe.H2O, Z-Gly-Ac3c-Gly-OTmb.(CH3)2CO, and t-Boc-(Ac3c)4-OMe.2H2O. Type-I (I') beta-bends and distorted 3(10)-helices were found to be typical of the tri- and tetrapeptides, respectively. In the dipeptides, too short to form beta-bend conformations, other less common structural features may be observed. The average geometry of the cyclopropyl moiety of the Ac3c residue is asymmetric and the N-C alpha-C' bond angle is significantly expanded from the regular tetrahedral value. A comparison with the structural preferences of other extensively investigated C alpha, alpha-dialylated alpha-amino acids is made and the implications for the use of the Ac3c residue in conformational design are examined.

Alkylation↗
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

The value of bone marrow biopsy in breast cancer at the time of first relapse. A prospective study.

The value of bone marrow biopsy (BMB) in advanced breast cancer at the time of first relapse was studied in a prospective manner. Bone marrow biopsy was performed in 142 consecutive unselected metastatic patients: 129 at the time of first recurrence, and 13 in patients with metastases at the time of first diagnosis. Overall, BMB was positive in 32 patients (23%). In the group with negative bone x-ray, it was positive in two patients of 84 (2%); both of them had doubtful scan. In the group with positive x-ray, BMB resulted positive in 30 of 58 (52%). There was a significant correlation between number of bone segments radiologically involved and BMB positivity rate, ranging from 15% in the patients with only one, to 68% in those with more than three sites involved (P = 0.02). Patients with x-ray evidence of metastases in the pelvis had significantly higher rate of BMB positivity (67% versus 32%; P = 0.02). The median survival time from the first relapse was 153 weeks in BMB-negative cases and 149 in positive ones. Considering only the patients with demonstration of bone invasion obtained with either or both x-ray and BMB, 34/62 patients had positive BMB (55%). In these cases BMB was found more often positive in patients 50 years or younger than in patients older than 50 years (80% versus 47%; P = 0.05); the median survival time was longer, but not significantly, in BMB-positive patients than in negative ones (149 weeks versus 119; P = 0.3). The authors conclude that BMB is not required in common restaging procedure when both bone survey and scan are negative. Bone marrow biopsy results are more often positive in younger patients and survival is not negatively affected by bone marrow invasion as diagnosed by BMB.

Biopsy↗
PubMed1988

The value of bone marrow biopsy in breast cancer at time of diagnosis. A prospective study.

Bone marrow biopsies (BMB) were performed in 173 consecutive unselected breast cancer patients at the time of diagnosis to define the value of this diagnostic tool in the initial staging of mammary carcinoma. In a group of 160 patients with a negative standard staging work-up, BMB was positive in two (1%). Both of them had negative x-ray but bone scan was positive in one and doubtful in the other. Bone marrow biopsy was positive in 31% of 13 additional patients with metastatic disease and in 44% of the nine among them with radiologically involved skeleton. These results exclude that BMB is able to discover micrometastatic foci of neoplastic disease. Its positivity appears strictly correlated with that of bone x-ray and scan. Based on the results of this prospective study, BMB is not required when both bone survey and scan are negative, but could be useful in clarifying diagnostic doubts of skeletal involvement.

Adult↗
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↗
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↗
PubMed1984

Problems in evaluating response of primary breast cancer to systemic therapy.

The evaluation of the response of primary breast cancer to systemic therapy is difficult. Evaluable primary lesions may be assessed both by physical and by mammographic examination. In this study, response to therapy was evaluated after 4 cycles of CMF or CMF plus tamoxifen in 49 patients with locally advanced breast cancer entering a prospective randomized trial. In 35 patients response was evaluated by both physical examination and mammography. In some cases there was disagreement between physical examination and mammography in quantifying the magnitude of response. In 8 of 35 (22.9%), the overall response was overestimated by physical examination versus mammography, while in 3 of 35 (8.6%) the reverse was true. Taking into consideration different criteria in attributing the overall response, i.e. selecting physical examination only, mammography only, or the most favorable or the least favorable response between the two methods of assessment, the objective remission rates were 65.7%, 54.3%, 71.4% and 45.7%, respectively. The data suggest that both physical examination and mammography should be used in evaluating the response of primary breast cancer to a systemic treatment. Should these two methods yield contrasting results, the data obtained with each method should be reported. The best observed response may be employed in determining the overall response.

Adult↗
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

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

Studies on gliadin related peptides. I. Synthesis, purification and 1H n.m.r. characterization of the pentapeptide H-Tyr-(Gln)3-Pro-OH.

The pentapeptide H-Tyr-(Gln)3-Pro-OH has been recently postulated to be the basic repetitive unit of a sequential polypeptide contained in wheat bread alpha-gliadins, which are believed to be toxic factors in coeliac disease, gluten-dependent enteropathy. Solid-phase synthesis, purification and 1H n.m.r. characterization in water solution of this peptide are described.

Chromatography, High Pressure Liquid↗
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↗
PubMed1982

Peptaibol antibiotics: a study on the helical structure of the 2-9 sequence of emerimicins III and IV.

Solution conformations of the protected 2-9 segment of the peptaibol antibiotics emerimicins III and IV [alpha-aminoisobutyric acid (Aib)]3-L-Val-Gly-L-Leu-(Aib)2 and the related short sequences benzyloxy-(Aib)3-L-Val-OMe and benzyloxy-(Aib)3-L-Val-Gly-OMe have been investigated by circular dichroism studies. For the latter two compounds the structural preferences in the solid state have been assayed by x-ray diffraction analyses. The experimental data described here, along with those previously reported, support the view that the shortest Aib-containing segments (from tri- through pentapeptides) adopt the 3(10)-helical structure both in solution and in the solid state. In contrast, the octapeptide appears to adopt the alpha-helical structure in solution. The role of peptide chain length and specific amino acid sequences in stabilizing either of the two helical structures and hence their possible implications on the nature of the channel formed by peptaibol antibiotics in the membrane are also briefly outlined.

Alkylation↗