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Find more information on the Altmetric Attention Score and how the score is calculated. Starting with the thienopyridinone derivative 26d T an optimization study was performed, which resulted in the identification of a highly potent and orally bioavailable LHRH receptor antagonist, 3- N -benzyl- N -methylaminomethyl 2,6-difluorobenzyl -4,7-dihydro[4- 1-hydroxycyclopropanecarboxamido phenyl]isobutyryloxothieno[2,3- b ]pyridine 33c.
Compound 33c displayed subnanomolar in vitro activities for the human receptor and its oral administration caused effective suppression of the plasma LH levels in castrated male cynomolgus monkeys. Furthermore, SAR studies revealed that a hydroxyalkylamido moiety on the 2-phenyl ring is virtually equivalent to an alkylureido moiety, at least in this series of compounds.
Elemental analysis data of new compounds. View Author Information. Cite this: J. Article Views Altmetric -.
Citations Supporting Information Available. Cited By. This article is cited by 13 publications. Journal of Medicinal Chemistry , 56 3 , Comparable differences were observed here in the kinetic properties of enzymes comprising cS40LH 6 and cL40S fusions, supporting the concept that engineering changes to the C terminus of L such as linking it to the N terminus of S invariably lead to reduced catalytic performance.
In contrast, there was no compromise in catalytic viability when adjoining the C terminus of S to the N terminus of L using flexible linker peptides Table 1 , indicating this is the favored configuration for linking these Rubisco subunits. Future Prospects for Rubisco Engineering in Higher Plants —Future work will assess the applicability of this linking strategy for assembling functional Rubisco complexes of linked higher plant Rubisco L and S in chloroplasts.
Further studies as to whether the chaperone complexes of higher plant plastids are capable of assembling these tobacco T S L L fusions into functional Rubisco complexes are obviously warranted. Successful replacement of the rbc L copy in the tobacco plastome with the comparable gene from sunflower 18 and the bacterium Rhodospirillum rubrum 15 , 17 by homologous replacement indicates that a comparable strategy for introducing the rbc T S40L or rbc T S60L genes is feasible.
Although transgenic manipulation by this means is a protracted process, it does provide a specific means by which to examine comprehensively the molecular, cellular, and physiological consequences of the transplanted fusion-Rubisco into plant plastids. That is, the kinetics of functional Rubisco fusions could be examined both in vitro after enzyme purification and in vivo using whole leaf gas exchange 15 — 17 , 20 , Moreover, such a transplantation would provide a means to assess whether the finding in this study that unassembled cyanobacterial S are excluded from assembling with C S60L fusions can be emulated in higher plant plastids.
Notably, in transplastomic tobacco expressing the Rubisco dimer L 2 from R. We thank John Andrews for valuable contribution to this research and Heather Kane for comments on the manuscript. The costs of publication of this article were defrayed in part by the payment of page charges. Section solely to indicate this fact. You'll be in good company. Journal of Lipid Research. Whitney 1 and Robert E. Previous Section Next Section. View this table: In this window In a new window. Previous Section. Andrews, T.
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