Syntheses of thyrotropin-releasing hormones (TRH) (Schaf) and related peptides

The syntheses of seven tripeptide isomers containing L -histidine, L -proline and L -glutamic acid residues, the same as found in the natural thyrotropin-releasing hormone (TRH), are reported. In addition L -pyroglutamyl-L -histidyl-L -proline and its amide as well as N^α-acetyl-L -glutamyl-L -histidyl-L -proline are described. Whereas eight peptides are inactive and L -pyroglutamyl-L -histidyl-L -proline shows a slight TRH activity, L -pyroglutamyl-L -histidyl-L -proline-amide has the full biological activity of the isolated thyrotropin-releasing hormone and, at the present state of knowledge, seems to be identical with it.     

An efficient synthesis of thyrotropin releasing hormone (TRH)

A convenient and simple synthesis of L -pyroglutamyl-L -histidyl-L -prolinamide is described. Two pathways using the solid phase technique have led to the pure tripeptide.     

The rotating ring-disk electrochemistry of the copper(II) complex of thyrotropin-releasing hormone

Thyrotropin-releasing hormone (TRH) forms an electroactive Cu(II) complex in aqueous solution. Rotating ring-disk electrochemistry reveals oxidation at the disk electrode and reduction at the ring electrode. The plot of limiting current vs. square root of rotation frequency deviates from the Levich equation, indicating both preceding and following chemical reactions. The reaction following the oxidation is a multiple-electron ECE-type of process that has been seen before in Cu(II)–peptide electrochemistry. The preceding reaction is unusual. The deviation from diffusion-controlled behavior is more pronounced at higher initial concentration of Cu(II) and peptide. We propose that a non-electroactive dimer, Cu(II)₂–TRH₂, is in a slow equilibrium with the electroactive Cu(II)–TRH. Simulation of the RRDE behavior of the postulated Cu(II)–TRH system has succeeded in matching experimental data. Capillary electrophoresis indicates that there is a negative charge on the dimer. It is suggested that a hydroxo-bridge may link the two Cu(II) centers. Calculations verify that bi-nuclear Cu(II)₂–TRH₂ complexes are possible.     

Enzyme immunoassay of thyrotropin releasing hormone (TRH).

A sensitive and specific double-antibody enzyme immunoassay (EIA) for a thyrotropin releasing hormone (TRH)-like immunoreactive substance has been developed. In order to synthesize TRH-labeled beta-D-galactosidase (beta-gal), a newly devised TRH derivative, pGlu-His-Pro-NH-(CH2)6-NH2 (TRH-Hex), was employed. TRH-Hex was linked to beta-gal by the N-(epsilon-maleimidocaproyloxy) succinimide coupling procedure. For competitive reactions, the TRH antibody was incubated with standard TRH and TRH-Hex-beta-gal (delayed addition). Free and antibody-bound enzyme hapten were separated by using an anti-rabbit immunoglobulin G coated immunoplate. Activity of the enzyme on the plate was fluorometrically determined. The present immunoassay allows detection of 0.8 to 100 pmol/well of TRH.     

Stereoselectivity in divalent cobalt,nickel and zinc bis complexes of some amino(methyl or benzyl) substituted histidines

Stability constants and stereoselective effects are presented for divalent Co, Ni and Zn complexes of histidine (H-his), α-N-methyl- (H-mhis), dimethyl- (H-dimhis) and benzylhistidine (H-bhis). In the zinc-dimethylhistidine system, species Zn(dimhis), Zn(dimhis)₂ and ZnOH(dimhis) are observed. In all other cases only the 1:1 complex MA and the 1:2 complex MA₂ are found. Corresponding complexes of histidine, methylhistidine and dimethylhistidine have nearly the same constants κ₁; corresponding complexes of histidine, methylhistidine and benzylhistidine show approximatively the same stability constants κ_2,DL. Stability constants indicate that large steric hindrance between the ligands is present in M(dimhis)₂. Probably, zinc is tetrahedrally coordinated in Zn(bhis)₂; it is the only case where a (small) negative stereoselective effect (in favour of the “racemic complex” {MLL + MDD}) is found. In all other cases positive effects are found (i.e. in favour of the “meso complex” MDL), the value for bis(dimethylhistidino)nickel (1·62 kcal/mol) being the largest measured. The enhancement of the stereoselective effect per methyl group for histidine, methylhistidine and dimethylhistidine is 0·37 kcal/mol for cobalt and 0·57 kcal/mol for nickel; the enhancement for zinc is about the same of that of cobalt. The PMR spectra of cobalt complexes of dimethylhistidino and methylhistidine are interpreted with the help of deuteromethyl histidine compounds; in these ligands also the 2-CH proton of the imidazole residue is partly deuterated. The stereoselective effects in the cobalt complexes are confirmed by the PMR results. The number of signals per group of protons is doubled for Co(mhis) and a multiple for the Co(mhis)₂ complexes, which is caused by the secondary nitrogen atom becoming a new asymmetry centre. The two dimethylhistidine ligands in the meso-complexes CoDL and NiDL, probably, are no longer equivalent. Another indication of stereoselectivity in the systems cobalt and nickel-methylhistidine and cobalt-dimethylhistidine is the systematic difference of the solubility of MLL (or MDD) in regard to M(rac-A)₂, the optically active complexes being much less soluble; furthermore, they cristallize very well. Some crystallographic data on the optically active complexes are presented. On the basis of the potentiometric and PMR results it is concluded that the positive stereoselective effects are due to the stability of the C_i (all-trans) meso complex MDL being larger than that of any of the C₂ complexes of the racemic mixture and the C_i (all-cis) meso complex.     

The (in)significance of apparent viscosity in full-scale municipal membrane bioreactors

Ten pilot and full-scale municipal membrane bioreactor (MBR) plants throughout Europe were investigated during the period 2007–2008 using the Delft Filtration Characterisation method. Next to information on filterability the data also contain the necessary information to determine the apparent viscosity of activated sludge. The aim of this study was to quantify variations in the apparent viscosity of activated sludge in pilot and full-scale municipal MBR plants and correlate them with membrane performance. A statistical analysis was carried out in order to quantify the significance of the correlations between apparent viscosity and activated sludge characteristics. The main factor influencing activated sludge's apparent viscosity was found to be total suspended solids. Temperature was found not to have a direct impact on apparent viscosity within the range of temperatures of the pilot and full-scale municipal MBR plants studied (9.7–27.4°C). In terms of the reversible fouling potential and membrane performance, activated sludge filterability and MBR plant membrane permeability were not statistically affected by activated sludge's apparent viscosity variations. Therefore, even if apparent viscosity plays a major role in terms of oxygen transfer efficiency, it is not relevant when optimising membrane fouling control and membrane performance of current, full-scale municipal MBR applications.     

Synthesis of thyrotropin-releasing hormone-related peptides using N alpha-tert-butyloxycarbonyl-omega-(N-tert-butyloxycarbonylcarbamoyl)- alpha-amino acids

Application of N alpha,Nca-di-tert-butyloxycarbonylhomoglutamine to synthesis of thyrotropin-releasing hormone (TRH) analogs was examined. The delta-lactam formation from homoglutaminylpeptides took place more easily than gamma-lactam formation from glutaminylpeptides in water or dioxane containing acetic acid. [pHgu1,Nva2]-TRH had dose-dependent antagonistic activity against pentobarbital anesthesia in mice, but almost no binding activity to TRH receptor in rat brain.     

"Click"-modification of a functionalized poly(3,4-ethylenedioxythiophene) (PEDOT) soluble in organic solvents

A PEDOT-based conductive copolymer soluble in organic solvents was synthesized electrochemically using dihexyl-EDOT and azidomethyl-EDOT as monomers and was successfully post-functionalized by "click"-cycloaddition reaction with a functionalized terminal alkyne under mild heterogeneous conditions.     

钾离子调控的1,5-萘基桥联双冠醚的"off-on-off"和"on-off-on"行为

报道了萘基桥联双苯并15-冠-5的合成,研究了K+调控的双冠醚自组装过程以及伴随的独特荧光行为.这种发光行为不仅可以模拟一个荧光"off-on-off"开关和一个荧光"on-off-on"开关,而且其组装模式和功能上类似于酶的二聚化过程.     

The significance of the CrO(4)2- chemical equilibrium HCr(4)- equilibrium in the determination of chromium(VI) by flame spectrometry

Chromium atomic absorption for Cr(VI) solutions in the air-acetylene and air-hydrogen flames is pH-dependent, but not in the nitrous oxide-acetylene flame. The effect is shown to occur as a result of the HCrO(-)(4) chemical equilibrium CrO(2-)(4) equilibrium, and may cause significant errors in the determination of chromium by atomic-absorption Spectrometry unless the pH of sample and standard solutions is controlled.