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991.
Hans Ulrich Stilz Wolfgang Guba Bernd Jablonka Melitta Just Otmar Klingler Wolfgang König Volkmar Wehner Gerhard Zoller 《International journal of peptide research and therapeutics》1998,5(2-3):215-221
Summary Antagonists of the platelet fibrinogen receptor (GP IIb/IIIa receptor) are expected to be a new promising class of antithrombotic
agents. The binding of fibrinogen to the fibrinogen receptor depends on an Arg-Gly-Asp-Ser (RGDS) tetrapeptide recognition
motif. Structural modifications of the RGDS lead have led to the discovery of a non-peptide RGD mimetic GP IIb/IIIa antagonist20 (S 1197). Compound20 inhibits dose-dependently and reversibly human platelet aggregation. Modeling studies based on structure-activity data revealed
the following structural features of the drug as important for receptor binding: the amidino group, the carboxylate group,
hydrophobic substitutions at the carboxyl-terminus and at the side chain carrying the positive charge, the carboxyl-terminal
NH group of the β-amino acid as a hydrogen bond donor and one oxygen atom of the hydantoin as a hydrogen bond acceptor. The
ethyl ester prodrug of20 (S 5740) is an orally active antithrombotic agent which has the potential to be used to treat and prevent thrombotic diseases
in humans. 相似文献
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993.
Zhu Genhai Bohnert Hans J. Jensen Richard G. Wildner Günter F. 《Photosynthesis research》1998,55(1):67-74
Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) (EC 4.1.1.39) not only catalyzes carboxylation and oxygenation of ribulose-1,5-bisphosphate (RuBP), but it can also act either as an epimerase or isomerase converting RuBP into xylulose-1,5-bisphosphate (XuBP) or 3-ketoarabinitol-1,5-bisphosphate (KABP), respectively, a process called misfire. XuBP is formed as a result of misprotonation at C3 of the RuBP-enediol. It is released from Rubisco active sites and accumulates in the reaction mixture. Increasing the amounts of CO2 or O2 decreases XuBP production. However, KABP synthesis, which has been proposed to be only a product due to C2 misprotonation of the RuBP-endiol, is dependent upon the presence of O2. KABP remains tightly bound to Rubisco active sites after its formation, causing the loss of Rubisco activity (fallover). The results suggest that the non-stabilized form of the peroxy-intermediate in the oxygenase reaction can be converted in a backreaction to KABP and molecular oxygen. The stabilization of the peroxy-intermediate due to the presence of Mn2+ instead of Mg2+ eliminates the formation of KABP. 相似文献
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Treatment of the cell wall-less mutant CW 15 of Chlamydomonasreinhardtii with human serum leads to a marked increase of thecell volume, followed by an irreversible cytolysis. Heat-inactivatedserum as a control reveals no cytotoxic effects on CW 15. Experimentswith C4-, properdin-, C3-, and factor H-depleted sera indicatethe alternative pathway of complement as being responsible forthe serum-mediated lysis. After immunofluorescence marking aswell as electromicroscopically after negative staining the membraneattacking complex of complement, C5b-9, could be demonstratedon the surface of CW 15. These results together with the observationthat cells of the wild-type strain 11-32c of C. reinhardtiiare not lysed by active serum suggest that only protoplastsof Chlamydomonas carry surface structures capable to activatethe alternative pathway of complement. In order to find out whether other cell wall mutants of C. reinhardtii,besides CW 15, can also activate the human complement system,we tested three strains each of the three known mutant categories.Strains CW 4, CW 9, and CW 19, representing category A, andstrains CW 3, CW 10, and CW 92, representing category C, andCW 8 and CW 18, accounting for category B, were cytolysed bynormal human serum. Only one type used in our experiments, CW20 of category B, resisted serum treatment, suggesting the needto redefine this category.
1This paper is dedicated to Professor Dr. Andr? Pirson on theoccasion of his 80th birthday (Received December 1, 1989; Accepted April 5, 1990) 相似文献
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