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Biomedical subjects

F Heitz

Publications and source records attributed to F Heitz.

At least 91 records · Page 5Linked to original sources
PubMed1988

Peptides mimicking the flap of human renin: synthesis, conformation, and antibody recognition.

Four peptides related to human renin flap region have been synthesized. Two of them are ring closed through appropriately designed disulfide bridges. Structure analysis involving IR and NMR techniques and recognition by polyclonal human renin antibodies provides support for a beta-hairpin secondary structure of the cyclized peptides identical with that presented by the flap section in the speculative human renin model [Blundell, T., Sibanda, B. L., & Pearl, L. (1983) Nature (London) 304, 273-275; Sibanda, B. L., Blundell, T., Hobart, P. M., Fogliano, M., Bindra, J. S., Dominy, B. W., & Chirgwin, J. M. (1984) FEBS Lett. 174, 102-111].

Antibodies↗
PubMed1988

Hydrodynamic properties of colicin A. Existence of a high-affinity lipid-binding site and oligomerization at acid pH.

The hydrodynamic properties of colicin A have been studied. The molecular mass of colicin A was determined from sedimentation equilibrium centrifugation to be 63 +/- 1.2 kDa, in agreement with that determined from the primary amino acid sequence [Morlon et al. (1983) J. Mol. Biol. 110, 271-289]. The sedimentation coefficient has been analyzed over a wide range of ionic strength (NaCl 0.06-0.56 M) and pH (8-4) and was found to remain almost constant. However, below pH 5 an oligomerization of colicin A to tetramers occurred. The frictional coefficient value indicated that the shape of the colicin A monomer was very asymmetric. Analysis of the pH dependence of circular dichroism of colicin A and of its COOH-terminal domain indicated that a sharp transition occurred between pH 4 and 3. This transition was very much reduced for the COOH-terminal domain in the presence of a non-ionic detergent. The presence of a lipid-binding site in colicin A at neutral pH was demonstrated both by hydrodynamic studies with micelles of n-hexadecanoyl and n-octadecanoylphosphocholine and by differential sensitivity to a proteolytic enzyme in the presence or absence of detergent micelles. About 75 molecules of lipid were bound under these conditions suggesting that colicin A was bound to lipid micelles. In contrast, at acid pH, in the presence of an excess of lipid the tetramer was dissociated into monomers complexed to 20-30 lipid molecules, indicating the exposure of a high-affinity lipid-binding site.

Bacteria↗
PubMed1988

Mixed monolayers of linear gramicidins and phospholipid. Surface pressure and surface potential studies.

The behavior of two gramicidins incorporated into lipid monolayers is analyzed on the basis of the force and surface potential area curves. It is shown that the position of the gramicidins (helical axis parallel or perpendicular to the interface) depends on the monolayer pressure and that these molecules are not miscible with dioleoylphosphatidylcholine. Surface potential measurements suggest the existence of a relationship between the single channel characteristics and the surface potential and indicate that the tryptophans are essential for lowering the lipid surface potential in agreement with the single channel behaviour of both gramicidin A and gramicidin M.

Gramicidin↗
PubMed1988

Ionophore properties of a synthetic alpha-helical transmembrane fragment of the mitochondrial H+ ATP synthetase of Saccharomyces cerevisiae. Comparison with alamethicin.

A 22-amino acid polypeptide was synthesized to model the central transmembrane segment of subunit 8 of the H+ ATP synthetase of Saccharomyces cerevisiae and to test ionophore properties. Solid-phase synthesis was conducted on benzhydrilamino resin, and purification followed by high pressure liquid chromatography allowed the isolation of the pure product whose NH2 terminal was acetylated and whose molecular weight determined by Fast Atomic Bombardment was the expected 2,666. The infrared spectrum of this peptide in the solid state reveals a fully alpha-helical conformation, whereas in low dielectric constant solvents the alpha-helical content is 60%, as determined by circular dichroism studies. Macroscopic current-voltage curves displayed by different planar lipid bilayers (monomyristoleoyl-glycerol and phosphatidylethanolamine) doped with this peptide suggest a weakly voltage-dependent conductance. Only one conductance level is observed in any given single-channel conductance experiment. However, a series of experiments shows a distribution of conductance states, most often 440 or 3,000 pS, and occasionally 80, 1,200, or 6,500 pS. This behavior contrasts with the usual behavior of alamethicin, chosen as a model of "aggregating-helices" ionophore and whose conductance fluctuates continually between substates, through uptake and release of monomers. Nevertheless, alamethicin too can display, under certain conditions, long-lived and mono-level conductance states similar to those reported here for the newly synthesized peptide. These properties could possibly be explained by the formation of large domains of helical rods with a set of allowed and independent ionic pathways.

Alamethicin↗
PubMed1988

Left ventricular diastolic function during the first month of life.

UNLABELLED: In order to assess possible changes in myocardial relaxation occurring during the neonatal period, M-mode echocardiograms were recorded serially in 9 normal term infants and in another group of 10 one-month-old infants. The tracings were studied with an M-mode calculator. Although individual variations were greater in the data collected during the first 24 h, no significant difference was found in the indices of diastolic function of the left ventricle during the first 4 days of age. The following changes were observed between data recorded at 4 days and 1 month, respectively: normalized peak rate of left ventricle filling, 4.03 vs. 4.71 cm/s; diastolic peak velocity of early posterior motion of aortic root, 1.89 vs. 5.15 cm/s; peak velocity of left ventricle posterior wall motion in diastole, 3.31 vs. 3.50 cm/s; mitral valve EF slope, 59.05 vs. 84.92 mm/s; left ventricle isometric relaxation time, 43.88 vs. 28.50 ms. IN CONCLUSION: (1) greater individual variations are observed in indices of left ventricle diastolic function during the first day of life, and (2) significant increase in left ventricle compliance occurs during the first month of life. These changes should play a critical role in the clinical course of newborn with cardiopulmonary disease.

Diastole↗
PubMed1987

Linear gramicidins at the air-water interface.

The behavior of four linear gramicidins, which differ by the nature of their 9, 11, 13, and 15 aromatic residues, together with a covalent "head to tail" retro GA-DAla-GA dimer, has been examined at the air-water interface. It is shown that all four "monomers" have almost the same molecular area, which is compatible with either a single-stranded or a double-stranded helical model, whereas it is suggested that retro GA-DAla-GA could adopt another conformation. The surface potential measurements agree with those of different groups of molecules characterized by their single-channel behaviors.

Gramicidin↗
PubMed1987

Synthesis and characterization of Tyr(Bzl)9,11,13,15 and Tyr9,11,13,15 gramicidin A.

Tyr(Bzl) and Tyr gramicidin A were prepared by the solid phase method using a 4-(oxymethyl)-Pam resin and Bpoc as alpha-amino-protecting group. The benzylated analog [Gr.T(Bzl)] was purified by chromatography on silica gel and then on LH60 Sephadex. Removal of benzyl groups was carried out by hydrogenolysis and the debenzylated derivative (Gr.T) was purified in the same way. Both gramicidins were checked and characterized by t.l.c., HPLC, circular dichroism, 1H n.m.r. and single channel measurements. CD spectra were found to be different for Gr.T(Bzl) and Gr.T and strongly dependent upon the solvent and the concentration. Single channel conductance of Gr. T is slightly lower than that of Gr.A (A Gr.T approximately equal to 0.7 A Gr.T).

Circular Dichroism↗
PubMed1987

Cyclic tetrapeptides with sequences related to HC toxin. Conformations and cation binding.

Peptides with sequences related to HC toxin (cyclo(LAla-DAla-L-Aoe-DPro] can adopt a conformation locked by three gamma turns. A "structure--spectroscopy characteristics" relationship is proposed. These peptides can complex Mg++ cations and the binding is accompanied by a transconformation of the peptide backbone. The relevance with the biological activity of the toxin is discussed.

Amino Acid Sequence↗
PubMed1987

[Pelvimetry using x-ray computed tomography].

The accuracy and the low radiation dosage administered when tomodensitometry is carried out for pelvimetry has led us to specify the use of this technique in every day practice. We propose to make is still more reliable and to simplify it. We have correlated the measurements obtained on the ultrasound screen with those that have been obtained by measuring the dried pelvis and have sought ways of measuring directly the three fundamental diameters of the pelvis. We have achieved exact measurements within one millimeter. This very precise correlation has been reproduced when we examined skeletons using the tomodensitometer. Then, when we checked again the accuracy of these measurements, we used the method on pregnant women. We have taken two views and two slices: an AP view to study the contents of the uterus and the morphology of the upper strait; a profile view to measure the diameter between the promontory of the sacrum and posterior surface of the symphysis, and we have programmed the two following slices: a perpendicular slice at the level of the upper strait measuring directly the transverse median diameter; another slice at the level of the sciatic spines to measure directly the diameter between these spines. We present this method because it is very simple and absolutely precise and gives all the information that is necessary. The patient does not have to stay still for long and only has a small dose of irradiation. This procedure does not need the use of conversion tables, nor parallel rulers nor standardisation.

Female↗
PubMed1986

Analysis of the ion transfer through the channel of 9,11,13,15-phenylalanylgramicidin A.

The behavior of an analogue of gramicidin A in which all four tryptophanyl residues are substituted by phenylalanyl and which shows a strong voltage effect on the single channel conductance is analyzed on the basis of a 'three-barrier--two-site' model. It is shown that in the gramicidin family the side chains of some amino acids, in spite of their location, which point outside the channel can play a major role in the binding of ions in the channel and thus can significantly modify the energy profile of the channel.

Biological Transport↗
PubMed1986

Conformations of gramicidin A and its 9,11,13,15-phenylalanyl analog in dimethyl sulfoxide and chloroform.

In order to understand the difference in single channel behavior of gramicidin A as compared to that of gramicidin M- which is the mirror image of gramicidin M (all four tryptophanyl residues substituted by phenylalanine), conformational investigations were made under several experimental conditions. It is shown that, when examined under identical conditions, both molecules adopt the same conformations which could be identified in dimethyl sulfoxide (DMSO) and chloroform. In DMSO the conformation is based on a succession of beta-turns while in chloroform gramicidin A and M- can adopt a dimeric hybrid structure: a double helix terminated by two single-stranded helices involving the N- and C-terminal parts, respectively. It is therefore concluded that the difference in the energy profile between both gramicidins which was deduced from the ion transfer data has its origin in the nature of the aromatic side chains.

Chloroform↗
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↗
PubMed1985

Secondary structure of the pore-forming colicin A and its C-terminal fragment. Experimental fact and structure prediction.

Conformational investigations, using circular dichroism, on the pore-forming protein, colicin A (Mr 60 000), and a C-terminal bromelain fragment (Mr 20 000) were undertaken to estimate their secondary structure and to search for pH-dependent conformational changes. Colicin A and the bromelain peptide are mainly alpha-helical with an enrichment of the alpha-helical content in the C-terminal domain carrying the ionophoric activity. The non-negligible beta-sheet structure in the C-terminal domain is unstable and is easily transformed into alpha-helix upon decreasing the polarity of the solvent. No evidence of pH-dependent conformational modification, correlated with modification of colicin A activity, could be obtained. The secondary structure estimated on the basis of experimental data favoured a model in which the pore is built of a minimal number of six transmembrane alpha-helical segments. Search for such segments in the amino acid sequence of the C-terminal domain of colicin A was carried out by combining secondary structure prediction methods with hydrophobicity and hydrophobic movement calculations. Similar calculations on the C-terminal domains of colicin E1 and IB indicate a common structure of the pores formed by colicin A, E1 and IB. Only two or three putative transmembrane segments could be selected in the sequences of colicin A, IB or E1. As a result, it is concluded that the channel is probably not built by a single colicin molecule but more likely by an oligomer.

Chemical Phenomena↗
PubMed1985

Bacterial lipopeptides induce ion-conducting pores in planar bilayers.

Bacterial lipopeptides, known for their antibiotic activities, have been tested for their ability to interact with lipid membranes. These lipopeptides, Iturin A, Bacillomycin L and D and Peptidolipin NA present analogous structural characteristics: a heptapeptidic cycle is linked to a hydrocarbon chain. We present evidence that these lipopeptides modify the conductance of planar bilayers by forming ion-conducting pores.

Anti-Bacterial Agents↗
PubMed1985

Echocardiographic assessment of left ventricular function in patients with hypokalemia.

Based on clinical and experimental data, a cardiomyopathic syndrome has been attributed to chronic hypokalemia. Analysis of the published data indicates the presence of numerous other complicating factors which might have compromised cardiac function. Echocardiographic studies on 5 children with lifelong (Bartter's syndrome, 3 cases; congenital renal alkalosis, 1 case) or prolonged (primary hyperaldosteronism, 1 case) hypokalemia did not reveal any abnormalities of myocardial performance, thus questioning the premise that hypokalemia causes cardiomyopathy.

Bartter Syndrome↗