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41.
We study the derived functors of Hom that are computed by using flat resolutions of Hom. These are denoted n. We compare these with the usual Extn's and show that 1⊂ Ext1and indicate (using MacLane's terminology) why the class of associated short exact sequences is a proper class. When the ring is a Dedekind domain we classify the N such that n(–, N) = 0 and show that unlike the situation for other classically defined right derived functors of Hom, Hom is not balanced relative to the two classes of modules that make 1 vanish. 相似文献
42.
Highlights? Crystallographic structure of NRPS adenylation and PCP domain interface ? NRPS adenylation C-terminal domain rotation creates appropriate PCP interface ? Mechanism-based inhibitor traps conformationally flexible proteins ? Structure-guided mutagenesis improves noncognate NRPS interactions 相似文献
43.
The tryptophan isomers of the cyclic tetrapeptide CJ-15,208, reported to be a kappa opioid receptor (KOR) antagonist [Saito, T.; Hirai, H.; Kim, Y. J.; Kojima, Y.; Matsunaga, Y.; Nishida, H.; Sakakibara, T.; Suga, O.; Sujaku, T.; Kojima, N. J. Antibiot. (Tokyo)2002, 55, 847-854.], were synthesized to determine the tryptophan stereochemistry in the natural product. A strategy was developed to select linear precursor peptides that favor cyclization using molecular modeling, and optimized cyclization conditions are reported. The optical rotation of the l-Trp isomer is consistent with that of the natural product. Unexpectedly both isomers exhibit similar nanomolar affinity for KOR. 相似文献
44.
Christopher D Sharp M Fowler TH Jackson IV J Houghton A Warren A Nanda I Chandler B Cappell A Long A Minagar JS Alexander 《BMC neuroscience》2003,4(1):1-5
L-glutamate, an excitatory neurotransmitter, binds to both ionotropic and metabotropic glutamate receptors. In certain parts of the brain the BBB contains two normally impermeable barriers: 1) cerebral endothelial barrier and 2) cerebral epithelial barrier. Human cerebral endothelial cells express NMDA receptors; however, to date, human cerebral epithelial cells (neuroepithelial cells) have not been shown to express NMDA receptor message or protein. In this study, human hypothalamic sections were examined for NMDA receptors (NMDAR) expression via immunohistochemistry and murine neuroepithelial cell line (V1) were examined for NMDAR via RT-PCR and Western analysis. We found that human cerebral epithelium express protein and cultured mouse neuroepithelial cells express both mRNA and protein for the NMDA receptor. These findings may have important consequences for neuroepithelial responses during excitotoxicity and in disease. 相似文献
45.
We have calculated the energies of six lowest optically allowed states of a direct exciton, in semiconductors with diamond and zinc-blended crystal structures, in the presence of an arbitrary magnetic field taking into account the effects of degeneracy and anisotropy of the valence bands, using a variational approach. Using the experimentally suggested values of the various Kohn-Luttinger parameters in GaAs, we have evaluated the energies of these levels. The values thus obtained are compared with those derived from magneto-reflection measurements in high-purity epitaxial layers of GaAs, and good agreement is found. 相似文献
46.
Leslie N. Aldrich Evan P. Lebois L. Michelle Lewis Colleen M. Niswender C. David Weaver P. Jeffrey Conn Craig W. Lindsley 《Tetrahedron letters》2009,50(2):212-2868
General, high-yielding MAOS protocols for the expedient synthesis of functionalized 3,6-disubstituted-[1,2,4]triazolo[4,3-b]pyridazines are described amenable to an iterative analog library synthesis strategy for the lead optimization of an M1 antagonist screening hit. Optimized compounds proved to be highly selective M1 antagonists. 相似文献
47.
Gang Zhang Courtney C. Aldrich 《Acta Crystallographica. Section C, Structural Chemistry》2019,75(8):1031-1035
Mycobacterium tuberculosis (Mtb), the principal etiological agent of tuberculosis (TB), infects over one‐quarter of humanity and is now the leading cause of infectious disease mortality by a single pathogen. Macozinone {2‐[4‐(cyclohexylmethyl)piperazin‐1‐yl]‐8‐nitro‐6‐(trifluoromethyl)‐4H‐1,3‐benzothiazin‐4‐one, C20H23F3N4O3S} is a promising new drug for treating drug‐sensitive and drug‐resistant TB that has successfully completed phase I clinical trials. We report the complete spectroscopic and structural characterization by 1H NMR, 13C NMR, HRMS, IR, and X‐ray crystallography. The cyclohexyl moiety is observed to be nearly perpendicular to the core formed by the 1,3‐benzothiazin‐4‐one and piperazine groups. The central piperazine ring adopts a slightly distorted chair conformation caused by sp2‐hybridization of the nitro N atom, which donates into the electron‐deficient 1,3‐benzothiazin‐4‐one group. 相似文献
48.
Joseph A. Buonomo Dr. Courtney C. Aldrich 《Angewandte Chemie (International ed. in English)》2015,54(44):13041-13044
The Mitsunobu reaction is renowned for its mild reaction conditions and broad substrate tolerance, but has limited utility in process chemistry and industrial applications due to poor atom economy and the generation of stoichiometric phosphine oxide and hydrazine by‐products that complicate purification. A catalytic Mitsunobu reaction using innocuous reagents to recycle these by‐products would overcome both of these shortcomings. Herein we report a protocol that is catalytic in phosphine (1‐phenylphospholane) employing phenylsilane to recycle the catalyst. Integration of this phosphine catalytic cycle with Taniguchi’s azocarboxylate catalytic system provided the first fully catalytic Mitsunobu reaction. 相似文献
49.
Expressions for the energies of the 3s, 3p and 3d states of a polaron, bound to a positively charged impurity ion in a polar crystal through a Coulomb potential, are obtained in analytic forms using perturbation theory. The values of these energies are calculated in several polar crystals. 相似文献
50.
Venkatraman L Aldrich CC Sherman DH Fecik RA 《The Journal of organic chemistry》2005,70(18):7267-7272
[reaction: see text] An improved synthesis of (3S)-3-dihydronarbonolide is reported that constitutes a formal total synthesis of the 14-membered macrolactone antibiotic narbonolide. The key step was an intramolecular Nozaki-Hiyama-Kishi coupling to accomplish macrocyclization in improved yield. The high level of convergence will also allow us to rapidly synthesize narbonolide analogues for the study of enzymes in the pikromycin biosynthetic pathway. 相似文献