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991.
992.
Filippo Favretto Dr. Michael Assfalg Dr. Mariana Gallo Prof. Daniel Oscar Cicero Dr. Mariapina D'Onofrio Prof. Henriette Molinari 《Chembiochem : a European journal of chemical biology》2013,14(14):1807-1819
Human liver fatty acid binding protein (hL‐FABP) has been reported to act as an intracellular shuttle of lipid molecules, thus playing a central role in systemic metabolic homeostasis. The involvement of hL‐FABP in the transport of bile salts has been postulated but scarcely investigated. Here we describe a thorough NMR investigation of glycocholate (GCA) binding to hL‐FABP. The protein molecule bound a single molecule of GCA, in contrast to the 1:2 stoichiometry observed with fatty acids. GCA was found to occupy the large internal cavity of hL‐FABP, without requiring major conformational rearrangement of the protein backbone; rather, this led to increased stability, similar to that estimated for the hL‐FABP:oleate complex. Fast‐timescale dynamics appeared not to be significantly perturbed in the presence of ligands. Slow motions (unlike for other proteins of the family) were retained or enhanced upon binding, consistent with a requirement for structural plasticity for promiscuous recognition. 相似文献
993.
Dr Niels Grabow David P. Martin Klaus‐Peter Schmitz Katrin Sternberg 《Journal of chemical technology and biotechnology (Oxford, Oxfordshire : 1986)》2010,85(6):744-751
Stents are structural implants with widespread clinical use in vascular intervention to re‐open stenotic vessels for the treatment of coronary artery disease and peripheral arterial occlusive disease. Apart from their mechanical function, current drug‐eluting stents (DES) utilize local drug delivery from a drug‐incorporated permanent polymer coating to prevent in‐stent restenosis. This delayed closure of the stented vessel is considered one of the major limitations of conventional bare metal stents (BMS). The long‐term safety of DES, however, is still under debate, with reported cases of delayed healing, late thrombosis and hypersensitivity demanding further evolution in this field. A promising approach to circumvent the limitations of first generation DES is the application of degradable polymer coatings in second generation DES, and fully absorbable polymer stents. From a materials and engineering perspective, this paper provides a mini‐review of current clinically relevant DES technology and recent advancements in the development of stents from degradable polymeric materials as an alternative to permanent BMS and DES. This review, includes work on degradable stents and coatings based on blends of polylactic acid and the microbially‐produced poly(4‐hydroxybutyrate). Copyright © 2009 Society of Chemical Industry 相似文献
994.
995.
996.
997.
Dr. Veronika Papoušková Dr. Pavel Kadeřávek Olga Otrusinová Alžbeta Rabatinová Dr. Hana Šanderová Jiří Nováček Dr. Libor Krásný Prof. Vladimír Sklenář Dr. Lukáš Žídek 《Chembiochem : a European journal of chemical biology》2013,14(14):1772-1779
The partially disordered δ subunit of RNA polymerase was studied by various NMR techniques. The structure of the well‐folded N‐terminal domain was determined based on inter‐proton distances in NOESY spectra. The obtained structural model was compared to the previously determined structure of a truncated construct (lacking the C‐terminal domain). Only marginal differences were identified, thus indicating that the first structural model was not significantly compromised by the absence of the C‐terminal domain. Various 15N relaxation experiments were employed to describe the flexibility of both domains. The relaxation data revealed that the C‐terminal domain is more flexible, but its flexibility is not uniform. By using paramagnetic labels, transient contacts of the C‐terminal tail with the N‐terminal domain and with itself were identified. A propensity of the C‐terminal domain to form β‐type structures was obtained by chemical shift analysis. Comparison with the paramagnetic relaxation enhancement indicated a well‐balanced interplay of repulsive and attractive electrostatic interactions governing the conformational behavior of the C‐terminal domain. The results showed that the δ subunit consists of a well‐ordered N‐terminal domain and a flexible C‐terminal domain that exhibits a complex hierarchy of partial ordering. 相似文献
998.
Dr. Eric Largy Wenbo Liu Abid Hasan Prof. David M. Perrin 《Chembiochem : a European journal of chemical biology》2013,14(16):2199-2208
Janus‐type nucleosides are heterocycles with two faces, each of which is designed to complement the H‐bonding interactions of natural nucleosides comprising a canonical Watson–Crick base pair. By intercepting all of the hydrogen bonds contained within the base pair, oligomeric Janus nucleosides are expected to achieve sequence‐specific DNA recognition through the formation of J‐loops that will be more stable than D‐loops, which simply replaces one base‐pair with another. Herein, we report the synthesis of a novel Janus‐AT nucleoside analogue, JAT, affixed on a carbocyclic analogue of deoxyribose that was converted to the corresponding phosphoramidite. A single JAT was successfully incorporated into a DNA strand by solid phase for targeting both A and T bases, and characterized through biophysical and computational methods. Experimental UV‐melting and circular dichroism data demonstrated that within the context of a standard duplex, JAT associates preferentially with T over A, and much more poorly with C and G. Density functional theory calculations confirm that the JAT structure is well suited to associate only with A and T thereby highlighting the importance of the electronic structure in terms of H‐bonding. Finally, molecular dynamics simulations validated the observation that JAT can substitute more effectively as an A‐analogue than as a T‐analogue without substantial distortion of the B‐helix. Overall, this new Janus nucleotide is a promising tool for the targeting of A–T base pairs in DNA, and will lead to the development of oligo‐Janus‐nucleotide strands for sequence‐specific DNA recognition. 相似文献
999.
1000.
Yi‐Hui Peng Dr. Mohane Selvaraj Coumar Jiun‐Shyang Leou Jian‐Sung Wu Dr. Hui‐Yi Shiao Dr. Chia‐Hui Lin Dr. Wen‐Hsing Lin Tzu Wen Lien Dr. Xin Chen Dr. John T.‐A. Hsu Dr. Yu‐Sheng Chao Dr. Chien‐Fu Huang Dr. Ping‐Chiang Lyu Dr. Hsing‐Pang Hsieh Dr. Su‐Ying Wu 《ChemMedChem》2010,5(10):1707-1716
The need to develop safer and more effective antidiabetic drugs is essential owing to the growth worldwide of the diabetic population. Targeting the PPAR receptor is one strategy for the treatment of diabetes; the PPAR agonists rosiglitazone and pioglitazone are already on the market. Here we report the identification of a potent PPAR agonist, 15 , whose PPARγ activation was more than 20 times better than that of rosiglitazone. Compound 15 was designed to incorporate an indole head with a carboxylic acid group, and 4‐phenylbenzophenone tail to achieve a PPARγ EC50 of 10 nM . Compound 15 showed the most potent PPARγ agonist activity among the compounds we investigated. To gain molecular insight into the improved potency of 15 , a structural biology study and binding energy calculations were carried out. Superimposition of the X‐ray structures of 15 and agonist 10 revealed that, even though they have the same indole head part, they adopt different conformations. The head part of 15 showed stronger interactions toward PPARγ; this could be due to the presence of the novel tail part 4‐phenylbenzophenone, which could enhance the binding efficiency of 15 to PPARγ. 相似文献