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Rezension zu: Ludwig Pauli, Studien zur Golasecca-Kultur. R��mische Mitteilungen Erg.- Heft 19 (1971). 167 Seiten, 44 Abbildungen und 43 Tafeln, Bonner Jahrb��cher, Bd. 173.1973: Bonner Jahrb��cher

Rezension zu: P. Meller Padovani, Le Stele villanoviane di Bologna. Archivi, collana di preistoria, di arte preistorica e primitiva, hrsg. E. Anati, Band 7. Centro Camuno di Studi Preistorici, Capo di Ponte (Brescia) 1977. 103 Seiten, 70 Abbildungen., Bonner Jahrbücher, Bd. 180.1980: Bonner Jahrbücher

The neuropeptide Y (NPY) Y4 receptor (Y4R) is involved in energy homeostasis and considered a potential drug target for the treatment of obesity. Only a few molecular tools, i.e., radiolabeled and fluorescent ligands, for the investigation of the Y4R were reported. Previously, [Lys4]hPP proved to be an appropriate full-length PP analog to prepare a fluorescent ligand by derivatization at the e-amino group. To preclude oxidation upon long-term storage, we replaced the two methionine residues in [Lys4]hPP by norleucine and prepared the corresponding [3H]propionylated ([3H]12) and cyanine labeled (13) peptides, which were characterized and compared with a set of reference compounds in binding (Y1, Y2, Y4, and Y5 receptors) and functional (luciferase gene reporter, beta-arrestin-1,2) Y4R assays. Both molecular probes proved to be useful in radiochemical and flow cytometric saturation and competition Y4R binding experiments. Most strikingly, there was a different influence of the composition of buffer on equil...

A quite simple procedure for the generation of a polarized antiproton beam could be worked out if antiprotons are produced with some polarization. In order to investigate this possibility measurements of the polarization of produced antiprotons have been started at a CERN/PS test beam. The polarization will be determined from the asymmetry of the elastic antiproton scattering at a liquid hydrogen target in the CNI region for which the analyzing power is well known. The data are under analysis and an additional measurement is done in 2018. Details on the experiment and the ongoing data analysis will be given.

A quite simple procedure for the generation of a polarized antiproton beam could be worked out if antiprotons are produced with some polarization. In order to investigate this possibility measurements of the polarization of produced antiprotons have been started at a CERN/PS test beam. The polarization will be determined from the asymmetry of the elastic antiproton scattering at a liquid hydrogen target in the CNI region for which the analyzing power is well known. The data are under analysis and an additional measurement is done in 2018. Details on the experiment and the ongoing data analysis will be given.

Analogues of the argininamide-type NPY Y1 receptor (Y1R) antagonist BIBP3226, bearing carbamoyl moieties at the guanidine group, revealed subnanomolar Ki values and caused depression of the maximal response to NPY (calcium assay) by up to 90% in a concentration- and time-dependent manner, suggesting insurmountable antagonism. To gain insight into the mechanism of binding of the synthesized compounds, a tritiated antagonist, (R)-N(α)-diphenylacetyl-N(ω)-[2-([2,3-(3)H]propionylamino)ethyl]aminocarbonyl-(4-hydroxybenzyl)arginin-amide ([(3)H]UR-MK299, [(3)H]38), was prepared. [(3)H]38 revealed a dissociation constant in the picomolar range (Kd 0.044 nM, SK-N-MC cells) and very high Y1R selectivity. Apart from superior affinity, a considerably lower target off-rate (t1/2 95 min) was characteristic of [(3)H]38 compared to that of the higher homologue containing a tetramethylene instead of an ethylene spacer (t1/2 3 min, Kd 2.0 nM). Y1R binding of [(3)H]38 was fully reversible and fully displaceable by nonpeptide antagonists and the agonist pNPY. Therefore, the insurmountable antagonism observed in the functional assay has to be attributed to the extended target-residence time, a phenomenon of relevance in drug research beyond the NPY receptor field.

The goal of the P349 experiment is to test whether the antiproton production process can be itself a source of antiproton polarization. In this article, we present the motivation and details of the performed measurement. We report on the status of the analysis focusing mainly on calibration of the drift chambers and 3d track reconstruction.

The diastereomeric mixture of d/l-2,7-diaminooctanedioyl-bis(YRLRY-NH2) (BVD-74D, 2) was described in the literature as a high affinity Y4 receptor agonist. Here we report on the synthesis and pharmacological characterization of the pure diastereomers (2R,7R)- and (2S,7S)-2 and a series of homo- and heterodimeric analogues in which octanedioic acid was used as an achiral linker. To investigate the role of the Arg residues, one or two arginines were replaced by Ala. Moreover, N(ω)-(6-aminohexylaminocarbonyl)Arg was introduced as an arginine replacement (17). (2R,7R)-2 was superior to (2S,7S)-2 in binding and functional cellular assays and equipotent with 17. [(3)H]Propionylation of one amino group in the linker of (2R,7R)-2 or at the primary amino group in 17 resulted in high affinity Y4R radioligands ([(3)H]-(2R,7R)-10, [(3)H]18) with subnanomolar Kd values.

Derivatization of biologically active peptides by conjugation with fluorophores or radionuclide-bearing moieties is an effective and commonly used approach to prepare molecular tools and diagnostic agents. Whereas lysine, cysteine, and N-terminal amino acids have been mostly used for peptide conjugation, we describe a new, widely applicable approach to peptide conjugation based on the nonclassical bioisosteric replacement of the guanidine group in arginine by a functionalized carbamoylguanidine moiety. Four arginine-containing peptide receptor ligands (angiotensin II, neurotensin(8-13), an analogue of the C-terminal pentapeptide of neuropeptide Y, and a neuropeptide FF analogue) were subject of this proof-of-concept study. The N(ω)-carbamoylated arginines, bearing spacers with a terminal amino group, were incorporated into the peptides by standard Fmoc solid phase peptide synthesis. The synthesized chemically stable peptide derivatives showed high receptor affinities with Ki values in the low nanomolar range, even when bulky fluorophores had been attached. Two new tritiated tracers for angiotensin and neurotensin receptors are described.

The $\vec{p}p \rightarrow pK^{+}��$ reaction has been measured with the COSY-TOF detector at a beam momentum of $2.7\,\mathrm{GeV}/c$. The polarized proton beam enables the measurement of the beam analyzing power by the asymmetry of the produced kaon ($A_N^{K}$). This observable allows the $p��$ spin triplet scattering length to be extracted for the first time model independently from the final-state interaction in the reaction. The obtained value is $a_{t} = (-2.55 ^{+0.72}_{-1.39} {}_{\textrm{stat.}} \pm 0.6_{\textrm{syst.}} \pm 0.3_{\textrm{theo.}})\mathrm{fm}$. This value is compatible with theoretical predictions and results from model-dependent analyses., Revised version as accepted for publication in PRC