ALBERT

All Library Books, journals and Electronic Records Telegrafenberg

feed icon rss

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    ISSN: 0948-5023
    Keywords: Keywords Grignard compounds, Diethylether, Schlenk equilibrium, DFT calculation, Solvent effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Density Functional calculations have been used to study the solvent effect of diethyl ether on the Schlenk equilibrium and the aggregation of Grignard reagents RMgX with R = Me, Et, Ph. Solvent stabilization of the Mg complexes of the first solvent is larger than that of the second one. The solvation energy decreases on going from the dihalides MgX2 to the monohalides RMgX to the diorganyl compounds MgR2. The calculations indicate that the energetic preference of the unsymmetrical species reduces upon solvation. The strong tendency to dimerization of the un- and partly solvated compound vanishes for the higher solvated cases.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 2
    ISSN: 1573-4951
    Keywords: G-protein-coupled receptor ; Hartree-Fock calculations ; Histamine H2 receptor ; Molecular mechanics ; Receptor models
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Summary In the first part (pp. 461–478 in this issue) of this study regarding the histamine H2 receptor agonistic binding site, the best possible interactions of histamine with an α-helical oligopeptide, mimicking a part of the fifth transmembrane α-helical domain (TM5) of the histamine H2 receptor, were considered. It was established that histamine can only bind via two H-bonds with a pure α-helical TM5, when the binding site consists of Tyr182/Asp186 and not of the Asp186/Thr190 couple. In this second part, two particular three-dimensional models of G-protein-coupled receptors previously reported in the literature are compared in relation to agonist binding at the histamine H2 receptor. The differences between these two receptor models are discussed in relation to the general benefits and limitations of such receptor models. Also the pros and cons of simplifying receptor models to a relatively easy-to-deal-with oligopeptide for mimicking agonistic binding to an agonistic binding site are addressed. Within complete receptor models, the simultaneous interaction of histamine with both TM3 and TM5 can be analysed. The earlier suggested three-point interaction of histamine with the histamine H2 receptor can be explored. Our results demonstrate that a three-point interaction cannot be established for the Asp98/Asp186/Thr190 binding site in either of the investigated receptor models, whereas histamine can form three H-bonds in case the agonistic binding site is constituted by the Asp98/Tyr182/Asp186 triplet. Furthermore this latter triplet is seen to be able to accommodate a series of substituted histamine analogues with known histamine H2 agonistic activity as well.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 3
    ISSN: 1573-4951
    Keywords: α-helical model system ; Conformational analysis ; Counterpoise method ; Hartree-Fock calculations ; Histamine H2 receptor ; Molecular mechanics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Summary Mutation studies on the histamine H2 receptor were reported by Gantz et al. [J. Biol. Chem., 267 (1992) 20840], which indicate that both the mutation of the fifth transmembrane Asp186 (to Ala186) alone or in combination with Thr190 (to Ala190) maintained, albeit partially, the cAMP response to histamine. Recently, we have shown that histamine binds to the histamine H2 receptor as a monocation in its proximal tautomeric form, and, moreover, we suggested that a proton is donated from the receptor towards the tele-position of the agonist, thereby triggering the biological effect [Nederkoorn et al., J. Mol. Graph., 12 (1994) 242; Eriks et al., Mol. Pharmacol., 44 (1993) 886]. These findings result in a close resemblance with the catalytic triad (consisting of Ser, His and Asp) found in serine proteases. Thr190 resembles a triad's serine residue closely, and could also act as a proton donor. However, the mutation of Thr190 to Ala190 — the latter is unable to function as a proton donor — does not completely abolish the agonistic cAMP response. At the fifth transmembrane α-helix of the histamine H2 receptor near the extracellular surface, another amino acid is present, i.e. Tyr182, so an alternative couple of amino acids, Tyr182 and Asp186, could constitute the histamine binding site at the fifth α-helix instead of the (mutated) couple Asp186 and Thr190. In the first part of our present study, this hypothesis is investigated with the aid of an oligopeptide with an α-helical backbone, which represents a part of the fifth transmembrane helix. Both molecular mechanics and ab initio data lead to the conclusion that the Tyr182/Asp186 couple is most likely to act as the binding site for the imidazole ring present in histamine.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 4
    ISSN: 1573-4951
    Keywords: Histamine ; H1-receptor ; H1-agonists ; H1-antagonists ; G-protein coupled receptor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Summary A modelling study has been carried out, investigating the binding of histamine (Hist), 2-methylhistamine (2-MeHist) and 2-phenylhistamine (2-PhHist) at two postulated agonistic binding sites on transmembrane domain 5 (TM5) of the histamine H1-receptor. For this purpose a conformational analysis study was performed on three particular residues of TM5, i.e., Lys200, Thr203 and Asn207, for which a functional role in binding has been proposed. The most favourable results were obtained for the interaction between Hist and the Lys200/Asn207 pair. Therefore, Lys200 was subsequently mutated and converted to an alanine, resulting in a 50-fold decrease of H1-receptor stimulation by histamine. Altogether, the data suggest that the Lys200/Asn207 pair is important for activation of the H1-receptor by histamine. In contrast, analogues of 2-PhHist seem to belong to a distinct subclass of histamine agonists and an alternative mode of binding is proposed in which the 2-phenyl ring binds to the same receptor location as one of the aromatic rings of classical histamine H1-antagonists. Subsequently, the binding modes of the agonists Hist, 2-MeHist and 2-PhHist and the H1-antagonist cyproheptadine were evaluated in three different seven-α-helical models of the H1-receptor built in homology with bacteriorhodopsin, but using three different alignments. Our findings suggest that the position of the carboxylate group of Asp116 (TM3) within the receptor pocket depends on whether an agonist or an antagonist binds to the protein; a conformational change of this aspartate residue upon agonist binding is expected to play an essential role in receptor stimulation.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...