Georg-Alexander Hoyer

Diosgenin saponins from Dioscorea floribunda

Abstract Five spirostanol glycosides and two furostanol glycosides were isolated from Dioscorea floribunda . In addition to the IR spectra of the free glycosides and the MS of the peracetates and permethyl ethers, the most effective method for structural determination proved to be the NMR spectra of the free saponins in pyridine- d 5 .

Sterile composition comprising a chelate complex for magnetic resonance imaging

A diagnostic medium contains at least one physiologically well tolerated complex salt comprising an anion of a complexing acid and one or more central ion or ions of an element with an atomic number of 21 to 29, 42, 44 or 57 to 83 and, optionally, one or more physiologically biocompatible cation or cations of an inorganic and/or organic base or amino acid, optionally, with additives customary in galenic formulations, dissolved or suspended in an aqueous medium.

Modeling and energy minimization studies on the herbicide binding protein (D1) in Photosystem II of plants

Abstract The herbicide binding site of the D1 protein in Photosystem II from spinach was modeled on the basis of the homologous L subunit of the photosynthetic reaction center of the bacterium Rhodopseudomonas viridis (Deisenhofer, J., Epp, O., Miki, K., Huber, R. and Michel, H. (1985) Nature 318, 618–624), and on the assignment of functional amino acid residues occurring in these two protein subunits. The overall structure of the L subunit with α-helices D, DE and E was assumed to be conserved in the D1 protein, although the loops connecting helices DE, E and D, DE were enlarged by 3 and 14 amino acid residues, respectively. Protein data bank searches for appropriate loop structures were performed, but none was found to be compatible with experimental data. The binding positions of some herbicides and of the natural substrate in the spinach Photosystem II are proposed and discussed in terms of different binding modes, and interpreted on the basis of data obtained from mutant D1 proteins.

Design of Inhibitors of Photosystem II using a Model of the D1 Protein

Several inhibitors belonging to structurally different chemical classes were used to analyze the predictive power of an initial model of the herbicide binding niche of the Dl protein belonging to photosystem II (PS II) from plants. In the case of small PS II inhibitors, the estimation of relative activities was hampered by uncertainty about the binding modes. To overcome this problem, a bulky substituent was introduced into the inhibitors to act as a hook, resulting in an unambiguous orientation in the model. The comparison of the modelling results and the experimentally determined IC 50 values of different triazines suggested that the previously assumed volume of the binding niche had to be reduced by 20%. After refinement of the model, it was possible to estimate qualitatively, the relative in-vitro activity for inhibitors belonging to different families, as long as an unambiguous binding mode could be deduced either from steric demands or from IC 50 values of mutant Dl proteins. The usefulness of the refined model is demonstrated by the successful de-novo design of a potent class of herbicides, the triazolopyrimidines.

Rational design of hirulog-type inhibitors of thrombin.

SummaryThe two crystal structures of thrombin complexed with its most potent natural inhibitor hirudin and with the active-site inhibitor d-Phe-Pro-Arg-CH2Cl [Rydel, T.J. et al., J. Mol. Biol., 221 (1991) 583; Bode, W. et al., EMBO J., 8 (1989) 3467] were used as a basis to design a new inhibitor, combining the high specificity of the polypeptide hirudin with the simpler chemistry of an organic compound. In the new inhibitor, the C-terminal amino acid residues 53–65 of hirudin are linked by a spacer peptide of four glycines to the active-site inhibitor NAPAP (Nα-(2-naphthyl-sulfonyl-glycyl)-dl-p-amidinophenylalanyl-piperidine). Energy minimization techniques served as a tool to determine the preferred configuration at the amidinophenylalanine and the modified piperidine moiety of the inhibitor. The predictions are supported by the interaction energies determined for d- and l-NAPAP in complex with thrombin, which are in good agreement with experimentally determined dissociation constants. The conformational flexibility of the linker peptide in the new inhibitors was investigated with molecular dynamics techniques. A correlation between the P1′ position and the interactions of the linker peptide with the protein is suggested. Modifications of the linker peptide are proposed based on the distribution of its main-chain torsion angles in order to enhance its binding to thrombin.

A side chain of diastereomeric iloprost protrudes from the cage in the complex with cyclomaltoheptaose (β-cyclodextrin): Crystal structure of (β-cyclodextrin)2 iloprost·20.5 H2O

Abstract A diastereomeric mixture of iloprost (16 R :16 S = 55:45) was co-crystallized with cyclomaltoheptaose (β-cyclodextrin, βCD) from aqueous solution as the complex (β-cyclodextrin) 2 ·iloprost·20.5 H 2 O. The crystals are triclinic P 1; a = 15.474(10), b = 15.446(10), c = 18.081(10) A, α = 99.40(3); β = 112.99(3), γ = 103.10(3)°. The βCD forms dimers with the O-2,3 sides hydrogen-bonded to each other. The dimers are arranged in layers in the ab plane and adjacent layers are shifted laterally so that the cavities of the dimers are closed by adjacent βCD molecules in a brick-type cage structure. The iloprost is disordered and identified only by a number of peaks of low electron density too close to be covalently bonded. The distribution of these peaks indicates that iloprost is partly included in the cavity of the dimer and that one of its side chains protrudes into the space between the dimers.