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121.
Benjamin E. Blass Pravin Iyer Magid Abou-Gharbia Wayne E. Childers John C. Gordon Mercy Ramanjulu George Morton Premkumar Arumugam Joshodeep Boruwa John Ellingboe Sayan Mitra Rajashekar Reddy Nimmareddy Shalini Paliwal Jamallamudi Rajasekhar Savithiri Shivakumar Pratima Srivastava Raghuram S. Tangirala Konda Venkataramanaiah L. Krishnakanth Reddy 《Bioorganic & medicinal chemistry letters》2018,28(13):2270-2274
The synthesis of steroid hormones is critical to human physiology and improper regulation of either the synthesis of these key molecules or activation of the associated receptors can lead to disease states. This has led to intense interest in developing compounds capable of modulating the synthesis of steroid hormones. Compounds capable of inhibiting Cyp19 (Aromatase), a key enzyme in the synthesis of estrogens, have been successfully employed as breast cancer therapies, while inhibitors of Cyp17 (17α-hydroxylase-17,20-lyase), a key enzyme in the synthesis of glucocorticoids, mineralocorticoids and steroidal sex hormones, are a key component of prostate cancer therapy. Inhibition of CYP17 has also been suggested as a possible target for the treatment of Cushing Syndrome and Metabolic Syndrome. We have identified two novel series of stilbene based CYP17 inhibitors and demonstrated that exemplary compounds in these series have pharmacokinetic properties consistent with orally delivered drugs. These findings suggest that compounds in these classes may be useful for the treatment of diseases and conditions associated with improper regulation of glucocorticoids synthesis and glucocorticoids receptor activation. 相似文献
122.
Stable coexistence of Rfi factors in Escherichia coli 总被引:7,自引:0,他引:7
123.
124.
Plant and Soil - The phenomenon of the compensation of growth factors is revealed with greatest clarity by partially cut forest stands. This paper reports the complete recovery of timber production... 相似文献
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126.
Santosh Kumar Srivastava V. Rajesh Iyer Tamoghna Ghosh Paramesh Ramulu Lambadi Ranjana Pathania Naveen Kumar Navani 《Nucleic acids research》2016,44(5):2451-2461
Advances in chemical biology have led to selection of synthetic functional nucleic acids for in vivo applications. Discovery of synthetic nucleic acid regulatory elements has been a long-standing goal of chemical biologists. Availability of vast genome level genetic resources has motivated efforts for discovery and understanding of inducible synthetic genetic regulatory elements. Such elements can lead to custom-design of switches and sensors, oscillators, digital logic evaluators and cell–cell communicators. Here, we describe a simple, robust and universally applicable module for discovery of inducible gene regulatory elements. The distinguishing feature is the use of a toxic peptide as a reporter to suppress the background of unwanted bacterial recombinants. Using this strategy, we show that it is possible to isolate genetic elements of non-genomic origin which specifically get activated in the presence of DNA gyrase A inhibitors belonging to fluoroquinolone (FQ) group of chemicals. Further, using a system level genetic resource, we prove that the genetic regulation is exerted through histone-like nucleoid structuring (H-NS) repressor protein. Till date, there are no reports of in vivo selection of non-genomic origin inducible regulatory promoter like elements. Our strategy opens an uncharted route to discover inducible synthetic regulatory elements from biologically-inspired nucleic acid sequences. 相似文献
127.
Characterization of Phase I and Phase II hepatic drug metabolism activities in a panel of human liver preparations. 总被引:2,自引:0,他引:2
The role of drug metabolism in drug discovery (lead compound selection) and the traditional role of identifying the enzymes involved in biotransformation pathways (reaction phenotyping) have both relied heavily on the availability and use of a human liver bank. The assessment of drug metabolizing enzyme activity and variability in a series of individual human livers is essential when characterizing the enzymes involved in metabolic pathways (i.e. correlation analysis). In this regard, a human liver bank of 21 samples (14 males, six females, and one unknown) was characterized with respect to the activity of several important drug metabolizing enzymes. The total CYP450 content of the livers ranged from 0.06 to 0.46 nmol/mg microsomal protein. The fold variations found in specific enzyme contents were as follows: CYP1A2 (3x), CYP2A6 (21x), CYP2C9 (8x), CYP2C19 (175x), CYP2D6 (18x), CYP2E1 (5x), CYP3A4 (18x), FMO (2.5x), UDPGT (4x), NAT (7x), COMT (5x), ST (5x), TPMT (3x), and GST (2.5x). In general, the fold variation of the Phase II enzymes was lower compared with the Phase I enzymes, with the exceptions of CYP1A2, CYP2E1, and FMO. Similar data were reviewed from other established liver banks and compared with regard to the relative variability observed in drug metabolizing capacities found in this study. 相似文献
128.
129.
Ali Bakr Joschka Hey Gianluca Sigismondo Chun-Shan Liu Ahmed Sadik Ashish Goyal Alice Cross Ramya Lakshmana Iyer Patrick Müller Max Trauernicht Kersten Breuer Pavlo Lutsik Christiane
A Opitz Jeroen Krijgsveld Dieter Weichenhan Christoph Plass Odilia Popanda Peter Schmezer 《Nucleic acids research》2021,49(20):11666
130.
Swagata Dasgupta Ganesh H. Iyer Stephen H. Bryant Charles E. Lawrence Jeffrey A. Bell 《Proteins》1997,28(4):494-514
A survey was compiled of several characteristics of the intersubunit contacts in 58 oligomeric proteins, and of the intermolecular contacts in the lattice for 223 protein crystal structures. The total number of atoms in contact and the secondary structure elements involved are similar in the two types of interfaces. Crystal contact patches are frequently smaller than patches involved in oligomer interfaces. Crystal contacts result from more numerous interactions by polar residues, compared with a tendency toward nonpolar amino acids at oligomer interfaces. Arginine is the only amino acid prominent in both types of interfaces. Potentials of mean force for residue–residue contacts at both crystal and oligomer interfaces were derived from comparison of the number of observed residue–residue interactions with the number expected by mass action. They show that hydrophobic interactions at oligomer interfaces favor aromatic amino acids and methionine over aliphatic amino acids; and that crystal contacts form in such a way as to avoid inclusion of hydrophobic interactions. They also suggest that complex salt bridges with certain amino acid compositions might be important in oligomer formation. For a protein that is recalcitrant to crystallization, substitution of lysine residues with arginine or glutamine is a recommended strategy. Proteins 28:494–514, 1997. © 1997 Wiley-Liss, Inc. 相似文献