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排序方式: 共有3696条查询结果,搜索用时 11 毫秒
91.
María Conde-Gimnez Juan Jos Galano-Frutos María Galiana-Cameo Alejandro Mahía Bruno L. Victor Sandra Salillas Adrin Velzquez-Campoy Rui M. M. Brito Jos Antonio Glvez María D. Díaz-de-Villegas Javier Sancho 《International journal of molecular sciences》2022,23(9)
Phenylketonuria (PKU) is a rare metabolic disease caused by variations in a human gene, PAH, encoding phenylalanine hydroxylase (PAH), and the enzyme converting the essential amino acid phenylalanine into tyrosine. Many PKU-causing variations compromise the conformational stability of the encoded enzyme, decreasing or abolishing its catalytic activity, and leading to an elevated concentration of phenylalanine in the blood, which is neurotoxic. Several therapeutic approaches have been developed to treat the more severe manifestations of the disorder, but they are either not entirely effective or difficult to adhere to throughout life. In a search for novel pharmacological chaperones to treat PKU, a lead compound was discovered (compound IV) that exhibited promising in vitro and in vivo chaperoning activity on PAH. The structure of the PAH-IV complex has been reported. Here, using alchemical free energy calculations (AFEC) on the structure of the PAH-IV complex, we design a new generation of compound IV-analogues with a higher affinity for the enzyme. Seventeen novel analogues were synthesized, and thermal shift and isothermal titration calorimetry (ITC) assays were performed to experimentally evaluate their stabilizing effect and their affinity for the enzyme. Most of the new derivatives bind to PAH tighter than lead compound IV and induce a greater thermostabilization of the enzyme upon binding. Importantly, the correspondence between the calculated alchemical binding free energies and the experimentally determined ΔΔGb values is excellent, which supports the use of AFEC to design pharmacological chaperones to treat PKU using the X-ray structure of their complexes with the target PAH enzyme. 相似文献
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Effect of P2O5 on the Structural and Magnetic Properties of Magnetite‐Based Glass‐Ceramics 下载免费PDF全文
Viorel Sandu Simona Greculeasa Andrei Kuncser Victor Kuncser 《Journal of the American Ceramic Society》2016,99(12):4013-4021
The specific morphology and magnetic properties of magnetite‐based glass‐ceramics obtained by crystallization of Fe‐containing borosilicate glassmelts in the presence of P2O5 as nucleating agent are investigated. We found that the distribution of the tiny nanoparticles of magnetite determines the low temperature response to magnetic field. The observed effects are discussed with respect to the following factors: (1) the existence of a multimodal size distribution of the tiny grains as revealed by Mössbauer spectroscopy, magnetometry, and high‐resolution electron microscopy; (2) the existence of a disordered layer at the grain surface which is driven by field in a magnetically ordered state; and (3) the interplay between the relaxation mechanisms in different temperature ranges. 相似文献
95.
Qilong Yuan I-Ming Chen Teguh Santoso Lembono Simon Nelson Landén Victor Malmgren 《Frontiers of Mechanical Engineering》2016,11(2):195-203
Covering objects with masking tapes is a common process for surface protection in processes like spray painting, plasma spraying, shot peening, etc. Manual taping is tedious and takes a lot of effort of the workers. The taping process is a special process which requires correct surface covering strategy and proper attachment of the masking tape for an efficient surface protection. We have introduced an automatic robot taping system consisting of a robot manipulator, a rotating platform, a 3D scanner and specially designed taping end-effectors. This paper mainly talks about the surface covering strategies for different classes of geometries. The methods and corresponding taping tools are introduced for taping of following classes of surfaces: Cylindrical/extended surfaces, freeform surfaces with no grooves, surfaces with grooves, and rotational symmetrical surfaces. A collision avoidance algorithm is introduced for the robot taping manipulation. With further improvements on segmenting surfaces of taping parts and tape cutting mechanisms, such taping solution with the taping tool and the taping methodology can be combined as a very useful and practical taping package to assist humans in this tedious and time costly work. 相似文献
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Nicolas Vivas Guy Bourgeois Christiane Vitry Yves Glories Victor de Freitas 《Journal of the science of food and agriculture》1996,72(3):309-317
The composition of various commercial tannin extracts were determined by liquid secondary ion mass spectrometry (LSIMS). Spectra were obtained directly from tannin extracts without any pre-separation. Eight different tannin powders were analysed: three gallotannins (Chinese, Turkish, tara), three ellagitannins (sweet chestnut, pendunculata oak, sessile oak), one mixed hydrolysable tannin (myrabolans) and one proanthocyanidin (grape seeds). This method enabled the main molecules in these powders to be identified. 相似文献
98.
Victor V. Dyakin Nuka V. Dyakina-Fagnano Laura B. Mcintire Vladimir N. Uversky 《International journal of molecular sciences》2022,23(1)
In humans, age-associated degrading changes, widely observed in molecular and cellular processes underly the time-dependent decline in spatial navigation, time perception, cognitive and psychological abilities, and memory. Cross-talk of biological, cognitive, and psychological clocks provides an integrative contribution to healthy and advanced aging. At the molecular level, genome, proteome, and lipidome instability are widely recognized as the primary causal factors in aging. We narrow attention to the roles of protein aging linked to prevalent amino acids chirality, enzymatic and spontaneous (non-enzymatic) post-translational modifications (PTMs SP), and non-equilibrium phase transitions. The homochirality of protein synthesis, resulting in the steady-state non-equilibrium condition of protein structure, makes them prone to multiple types of enzymatic and spontaneous PTMs, including racemization and isomerization. Spontaneous racemization leads to the loss of the balanced prevalent chirality. Advanced biological aging related to irreversible PTMs SP has been associated with the nontrivial interplay between somatic (molecular aging) and mental (psychological aging) health conditions. Through stress response systems (SRS), the environmental and psychological stressors contribute to the age-associated “collapse” of protein homochirality. The role of prevalent protein chirality and entropy of protein folding in biological aging is mainly overlooked. In a more generalized context, the time-dependent shift from enzymatic to the non-enzymatic transformation of biochirality might represent an important and yet underappreciated hallmark of aging. We provide the experimental arguments in support of the racemization theory of aging. 相似文献
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100.
Judit Olh Tibor Sznsi Attila Lehotzky Victor Norris Judit Ovdi 《International journal of molecular sciences》2022,23(3)
Protein–protein interactions (PPIs) outnumber proteins and are crucial to many fundamental processes; in consequence, PPIs are associated with several pathological conditions including neurodegeneration and modulating them by drugs constitutes a potentially major class of therapy. Classically, however, the discovery of small molecules for use as drugs entails targeting individual proteins rather than targeting PPIs. This is largely because discovering small molecules to modulate PPIs has been seen as extremely challenging. Here, we review the difficulties and limitations of strategies to discover drugs that target PPIs directly or indirectly, taking as examples the disordered proteins involved in neurodegenerative diseases. 相似文献