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Biomedical subjects

H Dürr

Publications and source records attributed to H Dürr.

At least 19 recordsLinked to original sources

An optomechanical transducer in the blue light receptor phototropin from Avena sativa.

The PHOT1 (NPH1) gene from Avena sativa specifies the blue light receptor for phototropism, phototropin, which comprises two FMN-binding LOV domains and a serine/threonine protein kinase domain. Light exposure is conducive to autophosphorylation of the protein kinase domain. We have reconstituted a recombinant LOV2 domain of A. sativa phototropin with various (13)C/(15)N-labeled isotopomers of the cofactor, FMN. The reconstituted protein samples were analyzed by NMR spectroscopy under dark and light conditions. Blue light irradiation is shown to result in the addition of a thiol group (cysteine 450) to the 4a position of the FMN chromophore. The adduct reverts spontaneously in the dark by elimination. The light-driven flavin adduct formation results in conformational modification, which was diagnosed by (1)H and (31)P NMR spectroscopy. This conformational change is proposed to initiate the transmission of the light signal via conformational modulation of the protein kinase domain conducive to autophosphorylation of NPH1.

Journal Article↗

A new photochromic 8pi-system based on an azaheptatriene-tetrahydroazepinoisoquinoline electrocyclization.

A new photochromic family of tetrahydroazepinoisoquinolines (THAI) 4a-i has been prepared. It undergoes light-induced ring opening from spiro compounds 4 to betaines 3 that decolorize in a very fast cyclizing reaction. Depending on substitution of the precursors 1 and 6, the photochromic styryltetrahydroindolizines (THI) 5k-q are formed in a periselective way. The conformation and configuration of the new photochromic THAI 4 and THI 5 were investigated by NMR and the structure of both compounds was proven by X-ray analysis. The photochromic properties were studied by laser flash photolysis, which afforded the lifetime of the colored form 3 and 3' in the micro- or nanosecond range.

Journal Article↗

Ruthenium polypyridine complexes. On the route to biomimetic assemblies as models for the photosynthetic reaction center.

We describe in this Account the preparation of RuL(3) complexes and their significance as biomimetic models for the photosynthetic reation center. Their preparation from simple or more complicated bypyridine ligands L and their photophysical data, especially their stability, are reported. Biomimetic models involving three concepts of the interaction of RuL(3) with acceptors in coordinatively, mechanically, or covalently linked supramolecular assemblies are also presented. The electron transfer (ET) of the noncovalently linked assemblies of RuL(3) complexes carrying polyether chains with one or two anisyl binding sites (4 or 5) with the cyclic bisviologen was studied. Molecular modeling and NMR titration clearly show the formation of supramolecular assemblies. Time-resolved spectroscopy demonstrated that ET and charge separation in the RuL(3) complexes with two binding sites are more efficient. The more constrained RuL(3)-bisviologen-catenane (6) possesses two conformations which exhibit different efficiency in ET, creating a charge-separated state in the microsecond domain. The covalently linked Ru(bpy)(3)(2+)-viologen assemblies having one (7, diad) or two bisviologen arms (8, diad) result in efficient ET. Addition of linear polyethers, cyclic polyethers, or crowns generates new triads and tetrads of the pseudorotaxane type. Molecular modeling and NMR titration clearly indicate the formation of supramolecular assemblies. The analysis of time-resolved studies proves fast ET and especially long-lived charge-separated states in these pseudorotaxanes. These data, compared with the findings for the photosynthetic reation center, show conclusive results. The lifetimes of the charge-separated states increase clearly in the sequence for noncovalently < mechanically < and covalently linked assemblies.

2,2'-Dipyridyl↗

[Sports in the heart rehabilitation group--experiences with ambulatory rehabilitation at home].

Regular physical exercise has shown to be beneficial for patients with cardiovascular disease. Therefore cardiac rehabilitation in Germany is continued for years after hospital discharge in outpatient cardiac exercise groups which meet twice a week under the guidance of a physician and a sports instructor. Before participation cardiac patients have to be examined including exercise tests and echocardiography for assessment of contraindications for exercise therapy as well as individual exercise capacity. Patients are assigned to two groups with different levels of exercise intensity according to their symptom-free work-capacity (cutoff level 1 W/kg). During exercise sessions sports-specific forms of exercise such as stretching, aerobic exercise or ball games are accompanied by psychosocial elements such as stress management. This global approach is intended to improve cardiovascular risk factors, cardiac function, and work capacity as well as to stabilize the patient psychologically in order to accelerate social integration. Recently these groups have opened towards patients after cardiac transplantation or with severe heart failure. Therefore, cardiac exercise groups play a central role in cardiac rehabilitation long after the acute cardiac event.

Ambulatory Care↗

Highland mountain hiking and coronary artery disease: exercise tolerance and effects on left ventricular function.

Physical exercise has become a well-established concept in the secondary prevention of coronary artery disease. We investigated the exercise requirements of extensive highland mountain hiking (8.7 km, 470 m to 1220 m over sea level, average incline 8.5%, mean walking velocity < 3 km x h-1) in 11 regularly exercising male patients with history of MI and stable coronary artery disease (CAD; mean age +/- SD:61.0 +/- 3.9 yr) and 9 age-matched male healthy controls (CO; mean age +/- SD:61.2 +/- 5.0 yr). All subjects underwent continuous ECG monitoring; arterial blood pressure and blood lactate concentrations were measured several times during mountain hiking. Before and after exercise, cardiac dimensions and functions were assessed by two-dimensional echocardiography and Doppler echocardiography. The mean exercise levels for heart rate and blood lactate were compared with the corresponding data of a multistage upright cycle ergometry. Clinical manifestations of coronary insufficiency, left ventricular myocardial dysfunction, or cardiac arrhythmias > Lown IIIb were not observed in any case. No significant differences in left atrial and left ventricular dimensions and no changes in systolic left ventricular function compared with the preexercise values were found after the mountain hike tour. Doppler echocardiography demonstrated significant changes in diastolic left ventricular function in CAD, but not in CO. The peak exercise intensity during mountain hiking was equivalent to a workload of 100-125 W (1.25-1.5 W x kg-1 body weight) in a multistage upright cycle ergometry. Extensive highland mountain hiking may be a low risk alternative within the outpatient rehabilitation program for secondary prevention of CAD for MI patients with a cycle ergometric exercise tolerance > 1.5 W x kg-1 body weight.

Aged↗

[Coronary circulation and metabolic function in endurance trained paraplegics].

OBJECTIVE: To determine the effect of physical activity on pulmonary, cardiovascular and metabolic activity in paraplegics. PATIENTS AND METHODS: Eight male paraplegics (average age 35.7 [range 25-47] years) had been selected from a pool of training members of the German Sport Union for the Disabled. They performed graded arm crank training for 8.3 +/- 3.1 h/week. Left ventricular volume (LVV), stroke volume (SV), wall thickness (WT), heart rate (HR) as well as serum lactate concentration were measured after different levels of the graded exercise. Results were compared with those obtained in 11 male sport students (average age 26.4 [23-30] years), who had similarly trained for 5.6 +/- 1.3 h/week. RESULTS: The paraplegics had a significantly smaller LVV than the controls (771 +/- 84 ml vs 976 +/- 84 ml) and smaller SV (83 +/- 13 ml vs 104 +/- 11ml), with comparable WT. Paraplegics achieved significantly lower maximal exercise (145 +/- 23.7 vs 160 +/- 28.2) and maximal HR (177 +/- 12 vs 170 +/- 9) were not significantly different at the various exercise steps. CONCLUSION: Paraplegia decreases cardiac dimensions and function. Long-term physical exercise achieves results comparable with those of untrained but not of trained healthy controls. Physically active paraplegics showed physiological cardiovascular and metabolic reactions to exercise.

Adult↗

Neuropeptide Y. Optimized solid-phase synthesis and conformational analysis in trifluoroethanol.

The 36-amino-acid neuropeptide Y (human), which is one of the most potent vasoconstrictors and which exhibits a number of other biological functions, has been synthesized using automated peptide synthesis. The optimized method, using 9-fluorenylmethoxycarbonyl protecting and single-step coupling, yielded the crude product in 90% purity allowing for single-step reversed-phase HPLC purification to greater than 98% purity and a high overall yield (50%). The hormone was characterized by several chromatographic methods, ion-spray mass spectroscopy and Edman degradation. The conformation of human neuropeptide Y was examined by CD, NMR and computer simulations. The CD measurements in trifluoroethanol/water (9:1) show a large percentage of alpha-helix. Variation of concentration, from 0.5 microM increasing up to the 1 mM used for NMR measurements, indicates no evidence for aggregation. In the same solvent system, the NMR line widths were very broad and therefore the resonance assignment was achieved with the exclusive use of two-dimensional NOE spectra. The 248 clearly distinguishable NOEs from the NMR study were used in distance geometry calculations and the resulting structures were refined with restrained molecular dynamics. The results indicate an alpha-helix extending from Arg19 to Gln34. For the N-terminal half of the molecule no regular structure was observed.

Amino Acid Sequence↗

Further characterization of neuropeptide Y receptor subtypes using centrally truncated analogs of neuropeptide Y: evidence for subtype-differentiating effects on affinity and intrinsic efficacy.

Previous attempts to classify neuropeptide Y receptor subtypes suffered from relying only on carboxyl-terminal analogs and fragments of neuropeptide Y. We have tested the potency and affinity of chemically different compounds, i.e., centrally truncated analogs of neuropeptide Y, in three Y1-like (Ca2+ mobilization in HEL cells, blood pressure increases in pithed rats, and 125I-neuropeptide Y binding in SK-N-MC cells) and two Y2-like (125I-neuropeptide Y binding to rabbit kidney membranes and presynaptic inhibition in rat vas deferens) model systems of neuropeptide Y receptors. Our data confirm the concept of two major subclasses of neuropeptide Y receptors, with some centrally truncated neuropeptide Y analogs having high affinity for Y2-like and low affinity for Y1-like neuropeptide Y receptors. Some of the truncated neuropeptide Y analogs are antagonists at Y1-like receptors and (possibly partial) agonists at Y2-like receptors. Our data also indicate that amino acid residues distal from the amino- and carboxyl-terminal ends of the peptide may subtype-selectively affect affinity and intrinsic efficacy of peptide agonists at neuropeptide Y receptors.

Amino Acid Sequence↗

Alpha-helical small molecular size analogues of neuropeptide Y: structure-activity relationships.

C-terminal analogues of neuropeptide Y (NPY) of small molecular size have been synthesized. The influence of chain length, single or multiple amino acid substitution, and segment substitutions on receptor binding, pre- and postsynaptic biological activity, and conformational properties have been investigated. Receptor binding and in vivo assays revealed biological activity for NPY Ac-25-36 that increased with increasing alpha-helicity. In attempts to stabilize the alpha-helical content, three independent types of modified NPY Ac-25-36 analogues were synthesized. Strong agonistic activities could be detected in a series of discontinuous analogues, which are constructs of N-terminal parts linked via different spacer molecules to C-terminal segments. One of the most active molecules was NPY 1-4-Aca-25-36 (Aca, epsilon-aminocaproic acid). For the first time conformational properties of a series of small NPY analogues have been investigated by CD, and correlated with biological activity and receptor binding. A C-terminal dodecapeptide segment of NPY with an amount of 50% substitution to the native C-terminal sequence of NPY was found to exhibit significant receptor binding.

Amino Acid Sequence↗

Cleavage kinetics and anchor linked intermediates in solid phase peptide amide synthesis.

Kinetics and cleavage conditions of peptide amide synthesis were studied using the anchor molecules 5-(4'-aminomethyl-3',5'-dimethoxyphenoxy)valeric acid (4-ADPV-OH) and 5-(2'-aminomethyl-3'-5'-dimethoxyphenoxy) valeric acid (2-ADPV-OH). Unexpectedly the anchor amide alanyl-4-ADPV-NH2 was isolated and characterized as an intermediate during the cleavage with trifluoroacetic acid (TFA) of alanyl-4-ADPV-alanyl-aminomethyl-polystyrene to yield the alanine amide. As a matter of fact the NH--CH alpha bond of the alanyl spacer has to be cleaved to form this intermediate. Using TFA-dichloromethane (1:9) alanyl-4-ADPV-NH2 was obtained as a cleavage product in 50% yield within 60 min, whereas the isomeric alanyl-2-ADPV-NH2 was formed more slowly under these mild conditions. At high TFA concentration no difference between the 2- and 4-ADPV anchor was observed in the rate of formation of the free alanine amide. The presence of tryptophan amide in the cleavage mixture resulted in an anchor alkylated tryptophan amide, which remains stable in acidic solution but disappears rapidly in the presence of the resin. A low TFA/high TFA cleavage procedure is recommended for peptide amid synthesis applying the ADPV anchor.

Alkylation↗