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J Verducci

Publications and source records attributed to J Verducci.

11 recordsLinked to original sources
PubMed2000

Anomeric effects in non-carbohydrate compounds: conformational differences between the oxazolidine rings of a cis-fused bicyclic system.

Tris(hydroxymethyl)aminomethane (Tris) can react with benzaldehyde (1:2 molar ratio) to produce cis-2,8-diphenyl-5-hydroxymethyl-1-aza-3,7-dioxabicyclo[3.3.0]octa ne, the structure of which has been confirmed by nuclear magnetic resonance spectroscopy and X-ray crystallography. The crystal structure showed that both oxazolidine rings A and B are puckered in opposite directions. Ring A exists in an E3 envelope form with 0-3 noticeably down (0.65 A) the plane of the remaining atoms, whereas ring B adopts the 7E envelope conformation with the 0-7 atom displaced up from the mean reference plane by 0.70 A. Comparison of bond angles and bond distances showed that both oxazolidine rings A and B exhibit cross endo-anomeric effects resulting from electron delocalization over the bond sequence O-3-C-2-N-1-C-8-O-7.

Bridged Bicyclo Compounds, Heterocyclic↗
PubMed2000

All-L-Leu-Pro-Leu-Pro: a challenging cyclization.

In this paper, we report the difficult synthesis of cyclo(Leu-Pro-Leu-Pro). While the cyclization of Leu-Pro-Leu-D-Pro did not cause problems, the all-L-peptide afforded cyclodimer rather than cyclotetrapeptide (cyclomonomer). A first attempt using our reversible backbone substitution methodology failed. However, we were successful in obtaining the desired cyclo(Leu-Pro-Leu-Pro) by decreasing the concentration. The ratio of cyclomonomer to cyclodimer was raised to 1:1.1 using BOP and 1:0.6 using HATU under our high dilution condition. The structures of the cyclopeptides were confidently assigned by electrospray ionization mass spectrometry and NMR.

Cell Division↗
PubMed1999

Comparison of indirect calorimetry, the Fick method, and prediction equations in estimating the energy requirements of critically ill patients.

BACKGROUND: Accurate measurement of resting energy expenditure (REE) is helpful in determining the energy needs of critically ill patients requiring nutritional support. Currently, the most accurate clinical tool used to measure REE is indirect calorimetry, which is expensive, requires trained personnel, and has significant error at higher inspired oxygen concentrations. OBJECTIVE: The purpose of this study was to compare REE measured by indirect calorimetry with REE calculated by using the Fick method and prediction equations by Harris-Benedict, Ireton-Jones, Fusco, and Frankenfield. DESIGN: REEs of 36 patients [12 men and 24 women, mean age 58+/-22 y and mean Acute Physiology and Chronic Health Evaluation II score 22+/-8] in a hospital intensive care unit and receiving mechanical ventilation and total parenteral nutrition (TPN) were measured for > or = 15 min by using indirect calorimetry and compared with REEs calculated from a mean of 2 sets of hemodynamic measurements taken during the metabolic testing period with an oximetric pulmonary artery catheter. RESULTS: Mean REE by indirect calorimetry was 8381+/-1940 kJ/d and correlated poorly with the other methods tested (r = 0.057-0.154). This correlation did not improve after adjusting for changes in respiratory quotient (r2 = 0.28). CONCLUSIONS: These data do not support previous findings showing a strong correlation between REE determined by the Fick method and other prediction equations and indirect calorimetry. In critically ill patients receiving TPN, indirect calorimetry, if available, remains the most appropriate clinical tool for accurate measurement of REE.

APACHE↗
PubMed1997

Metabolism of tentoxin by hepatic cytochrome P-450 3A isozymes.

The interaction between rat and human liver cytochrome P-450 with tentoxin, a natural phytotoxic cyclotetrapeptide having chlorotic properties, was studied by difference ultraviolet visible spectroscopy. Tentoxin interacted with rat liver microsomes and the difference spectrum was characteristic of binding to a protein site close to the heme. The intensity of this spectrum was clearly dependent on the amounts of P-450 3A in the microsomes and was optimal in dexamethasone-treated rat microsomes. Tentoxin exhibited a high affinity for P-450 3A (Ks approximately 10 microM). Similar results were observed with human P-450 isozymes expressed in yeast. Only P-450 3A4 and 3A5 were able to give spectral interactions with tentoxin. Liver microsomes from rats pretreated with dexamethasone, a specific inducer of P-450 3A, were found to be particularly active for the oxidation of tentoxin, which occurs mainly on its Ala(Me) function leading to demethylation. Yeast-expressed P-450 3A also exhibited high activity to metabolize tentoxin. The metabolites were identified by their ultraviolet and mass spectra in fast atom bombardment and collision-activated dissociation modes. In addition to the major N-demethylated metabolite, other hydroxylated metabolites were formed. Preliminary analysis showed that as tentoxin, some metabolites were still efficient chloroplast ATPase inhibitors, while at least one of them exhibited even at low concentration stimulatory effects.

Animals↗
PubMed1997

Destruxin analogs: variations of the alpha-hydroxy acid side chain.

This work describes the synthesis of three destruxin E cyclodepsipeptidic analogs. These compounds have an identical amino acid sequence but differ by the nature of the hydroxy acid residue with is 2-hydroxy-3-phenylpropionic (Hpp), 2-hydroxy-5-trimethylsilyl-4-pentynoic (Hpy-TMS) and 2-hydroxy-4-pentynoic (Hpy) acid, respectively. The insecticidal properties on the Galleria mellonella larvae (paralysis and lethal effect) of these analogs are presented in comparison with the natural destruxin E. All these compounds have toxic effects, the most potent being Hpy that induces the same effect as destruxin E.

Animals↗
PubMed1996

Tentoxin has at least two binding sites on CF1 and epsilon-depleted CF1 ATPases isolated from spinach chloroplast.

A new procedure for synthesis of 14C-labeled tentoxin [14C-MePhe[(Z)delta]3-tentoxin], with a high specific activity, is described. Binding experiments with CF1 or CF1-epsilon isolated from spinach chloroplast have been carried out using equilibrium dialysis technique. The results show the presence of two classes of binding sites. The association constants of the two major binding sites were derived from non-linear fitting of the binding curves. At 4 degrees C, the first binding site has a value of Ka1 = 8.2 x 10(5) M(-1) in CF1 and 8.7 x 10(5) M(-1) in CF1-epsilon, while the second binding site has lower affinity with Ka2 = 1.5 x 10(4) M(-1) in CF1 and 2.3 x 10(3) M(-1) in CF1-epsilon.

Binding Sites↗
PubMed1996

Synthesis, structure, and properties of MeSer1-tentoxin, a new cyclic tetrapeptide which interacts specifically with chloroplast F1 H(+)-ATPase differentiation of inhibitory and stimulating effects.

A new tentoxin analogue, in which the L-methyl alanine residue is substituted by L-methylserine, has been prepared following the synthetic pathway recently described for the synthesis of tentoxin [Cavelier, F., & Verducci, J. (1995) Tetrahedron Lett. 36, 4425-4428]. Using two-dimensional homonuclear proton nuclear magnetic resonance and structural analysis, we observed that MeSer1-tentoxin, like tentoxin, adopts several conformations in aqueous solution and presents self-aggregative properties. This analogue was found to be conformationally similar to the natural toxin. It showed the same efficiency as tentoxin in inhibition of ATPase activity of the isolated chloroplast F1 proton ATPase (CF1) as well as in inhibition of the ATP synthase activity of the membrane-bound enzyme (CF0CF1) in thylakoids and proteoliposomes. At concentrations above 10 microM, MeSer1-tentoxin did not reactivate CF1 to a high extent, contrary to tentoxin. It appeared, however, to bind in the same way, since the reactivating effect of tentoxin was inhibited by MeSer1-tentoxin. These results show that it is possible, using tentoxin analogues, to separate inhibitory and activating effects on the chloroplast ATPase, despite the limited chemical difference between the two toxins.

Adenosine Triphosphate↗
PubMed1993

Synthesis and biological activity of a destruxin analogue: D-Lac-6 destruxin E.

A general strategy for the synthesis of destruxin analogues is described and applied to a particular example, D-Lac-6 destruxin E. The tetrapeptide Boc-Ile-N-MeVal-N-MeAla-beta-Ala-OMe (2) was chosen as the basic starting compound, and its preparation was optimized. This fragment was then coupled with the compound (D)Lac-Pro, and the resulting peptide was cyclized by the DEPC or DPPA/HOBt/DMAP methods at 21 and 30% yield, respectively. The biological activity of the analogue obtained was established by injection to an insect host.

Amino Acid Sequence↗
PubMed1989

Ionic pores formed by cyclic peptides.

It is shown that 2 cyclic tetrapeptides, namely tentoxin and HC toxin, are able to induce the formation of transmembrane ionic channels, although a carrier mechanism could be expected on the basis of their chemical structure (presence of proline or N-methylated residues). Since other cyclic peptides but of larger size, i.e., tyrocidines, gramicidin S (decapeptides) and an octapeptide with a sequence similar to that of HC toxin, are also able to form pores, it appears that this property can be extended to a large number of cyclic peptides. A pore structure based on aggregates is proposed.

Circular Dichroism↗
PubMed1986

Aggregation and ion transfer induced by tentoxin.

It is shown that tentoxin, a cyclic tetrapeptide with two N-methylated residues, is able, when added to lipid bilayers, to increase the transmembrane current through discrete events. Conformational investigations involving 1H-NMR, infrared and circular dichroism studies show that, at concentrations above 7 X 10(-5) M, the cyclic tetrapeptide aggregates in chloroform. We suggest that the aggregates could form a pore through a stacking of cycles.

Circular Dichroism↗