Browsing by Subject "crystal structure"

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    Crystal structure of the N domain of human somatic angiotensin I-converting enzyme provides a structural basis for domain-specific inhibitor design
    (Elsevier, 2006) Corradi, Hazel R; Schwager, Sylva L U; Nchinda, Aloysius T; Sturrock, Edward D; Acharya, K Ravi
    Human somatic angiotensin I-converting enzyme (sACE) is a key regulator of blood pressure and an important drug target for combating cardiovascular and renal disease. sACE comprises two homologous metallopeptidase domains, N and C, joined by an inter-domain linker. Both domains are capable of cleaving the two hemoregulatory peptides angiotensin I and bradykinin, but differ in their affinities for a range of other substrates and inhibitors. Previously we determined the structure of testis ACE (C domain); here we present the crystal structure of the N domain of sACE (both in the presence and absence of the antihypertensive drug lisinopril) in order to aid the understanding of how these two domains differ in specificity and function. In addition, the structure of most of the inter-domain linker allows us to propose relative domain positions for sACE that may contribute to the domain cooperativity. The structure now provides a platform for the design of “domain-specific” second-generation ACE inhibitors.
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    Inclusion of the insecticide fenitrothion in dimethylated-β-cyclodextrin: unusual guest disorder in the solid state and efficient retardation of the hydrolysis rate of the complexed guest in alkaline solution
    (2013) Cruickshank, Dyanne L; Rougier, Natalia M; Vico, Raquel V; Bourne, Susan A; Buján, Elba I; Caira, Mino R; de Rossi, Rita H
    An anhydrous 1:1 crystalline inclusion complex between the organophosphorus insecticide fenitrothion [O,O-dimethyl O-(3-methyl-4-nitrophenyl)phosphorothioate] and the host compound heptakis(2,6-di-O-methyl)-β-cyclodextrin (DIMEB) was prepared and its structure elucidated by single-crystal X-ray diffraction. This revealed two independent host molecules in the asymmetric unit. In one of these, the cavity is occupied by two disordered guest components (distinguishable as rotamers with respect to the P–OAr bond) while in the other, three distinct guest components with site-occupancies 0.44, 0.29 and 0.27 appear, the last having a reversed orientation relative to all the other components. Kinetic studies of the alkaline hydrolysis of fenitrothion in the presence of DIMEB showed a remarkable reduction of 84% in the rate of this reaction relative to that for the free substrate, a value exceeding those previously attained with the native hosts, β- and γ-cyclodextrin, and fully methylated β-cyclodextrin.
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    Synthesis and X-ray structure of a new pyrrolo[1,2-b]-pyridazine derivative
    (2005) Caira, Mino R; Dumitrascu, Florea; Draghici, Constantin; Dumitrescu, Denisa; Cristea, Mihaela
    The synthesis, characterization and X-ray crystal structure of 2-(4-chloro-phenyl)-7-methylpyrrolo[1,2-b]pyridazine are reported. The compound crystallizes in the space group P21/c (No.14) with a =3.8568(1), b = 11.0690(3), c = 26.4243(7) Å, β = 92.777(1)° and Z = 4. Accurate molecular parameters for the novel heterocyclic system were obtained from intensity data collected at 113K. The molecule assumes a planar conformation in the crystal and the packing is based on π-π stacking with interplanar spacing 3.400 Å, typical of aromatic molecules with potential for displaying useful optical properties.
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    The X-ray crystal structures of ambraketal and 8-epi-ambraketal
    (Science Reviews 2000 Ltd, 2003) Gray, Christopher A; Davies-Coleman, Michael T; Caira, Mino R; Nathansona, Carole A; Wisch, Gregory A
    The crystal structures of ambraketal and 8-epi-ambraketal, synthesised in five steps from (–)-sclareol, are reported. Ambergris, a concretion formed in the intestinal tract of the blue sperm whale, has been used by perfumers since ancient times because of its unique fragrance and fixative properties.1 Restrictions imposed upon the whaling industry, in an attempt to protect these endangered marine mammals, have forced chemists to make synthetic substitutes for ambergris. Among these synthetic substitutes, the two epimeric bisnorlabdane acetals ambraketal (1; amberketal, ambracetal) and 8-epiambraketal (2, epi-amberketal, 8-epi-ambracetal, isoambraketal) have found prominence due to their strong fragrance and fixative properties respectively. Compounds 1 and 2 have also been reported as minor constituents in the bark of the western white pine tree (Pinus monticola).2