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51.
《Peptides》2014
The frog skin host-defense peptide tigerinin-1R (RVCSAIPLPICH.NH2) is insulinotropic both in vitro and in vivo. This study investigates the effects on insulin release and cytotoxicity of changes in cationicity and hydrophobicity produced by selected substitutions of amino acids by l-arginine, l-lysine and l-tryptophan. The [A5W], [L8W] and [I10W] analogs produced a significant (P < 0.01) increase in the rate of insulin release from BRIN-BD11 rat clonal β cells at concentration of 0.01 nM compared with 0.1 nM for tigerinin-1R. The increase in the rate of insulin release produced by a 3 μM concentration of the [S4R], [H12K], and [I10W] analogs from both BRIN-BD11 cells and mouse islets was significantly greater (P < 0.05) than that produced by tigerinin-1R. No peptide stimulated the release of lactate dehydrogenase at concentrations up to 3 μM indicating that plasma membrane integrity had been preserved. [A5W] tigerinin-1R was the only analog tested that showed cytotoxic activity against human erythrocytes (LC50 = 265 ± 16 μM) and inhibited growth of Escherichia coli (MIC = 500 μM) and Staphylococcus aureus (MIC = 250 μM). The circular dichroism spectra of tigerinin-1R and [A5W] tigerinin-1R indicate that the peptides adopt a mixture of β-sheet, random coil and reverse β-turn conformations in 50% trifluoroethanol/water and methanol/water. Administration of [S4R] tigerinin-1R (75 nmol/kg body weight) to high-fat fed mice with insulin resistance significantly (P < 0.05) enhanced insulin release and improved glucose tolerance over a 60 min period following an intraperitoneal glucose load. The study supports the claim that tigerinin-1R shows potential for development into novel therapeutic agents for treatment of type 2 diabetes mellitus. 相似文献
52.
H. Bayo Lawal 《Biometrical journal. Biometrische Zeitschrift》1993,35(5):589-599
The behavior of Pearson's X2 test, the likelihood ratio test Y2 and the two of its derivatives, G2 and Gk2, the Freeman-Tukey test (FT) and the Cressie and Read test Statistic I(2/3) are examined in this study. Estimated attained α levels based on 1000 simulated samples when the approximating distribution is χk-12, are computed for these tests for the various values of k, n and seven null hypotheses. Results from estimated power computations indicate that none of the test statistics has a clear advantage over any others, and that the choice of which test to use must therefore rest mainly on the performances with regards to the attained α levels when the χ2 approximation is invoked. In this respect, the log-normal approximation proposed by Lawal and Upton (1980) is strongly recommended. This is closely followed by the I(2/3). 相似文献
53.
54.
G Knowles B M Dutia E J Glass L MacCarthy-Morrogh R L Spooner J Hopkins 《Animal genetics》1994,25(3):129-131
An immunoblotting technique is reported that reveals electrophoretic variants in the β-chains of class II antigens of the bovine major histocompatibility complex. One monoclonal antibody, mAb VPM57, reacted on immunoblots with an epitope present in approximately half of the haplotypes investigated. This reagent is especially useful in discriminating electrophoretic variants that have similar isoelectric points. 相似文献
55.
56.
《Bioorganic & medicinal chemistry letters》2014,24(8):1923-1927
Herein we describe the design of a novel series of ATP competitive B-Raf inhibitors via structure-based methods. These 3-N-methylquinazoline-4(3H)-one based inhibitors exhibit both excellent cellular potency and striking B-Raf selectivity. Optimization led to the identification of compound 16, a potent, selective and orally available agent with excellent pharmacokinetic properties and robust tumor growth inhibition in xenograft studies. Our work also demonstrates that by replacing an aryl amide with an aryl sulfonamide, a multikinase inhibitor such as AZ-628, can be converted to a selective B-Raf inhibitor, a finding that should have broad application in kinase drug discovery. 相似文献
57.
《Bioorganic & medicinal chemistry letters》2014,24(16):3683-3689
Bacterial resistance is inevitable and is a growing concern. It can be addressed only by discovery and development of new agents. However the discovery and development of new antibacterial agents are at an all time low. This article broadly examines the historical as well as current status of antibacterial discovery and provides some perspective as how to address some of the challenges. 相似文献
58.
To determine how ligand-receptor interaction is affected by the charges of the amino acids at position 2 of the ligands and position 297 of the AT2 receptor, we generated the Asp297Lys mutant of AT2 and a ligand SarAsp2Ile. Asp297Lys mutant lost affinity to Ang II and SarIle however retained partial affinity to 125I-CGP42112A. The SarAsp2Ile had high affinity to Asp297Lys (IC503.5nM) and partial affinity to the AT2 (IC5015nM). Therefore, not only the charge, but also the length of the side arms of the amino acids at position 2 of the ligand and position 297 of the receptor affect their interaction. 相似文献
59.
Advances in salivary bioscience enable the widespread integration of biological measures into the behavioral and social sciences. While theoretical integration has progressed, much less attention has focused on analytical strategies and tactics. The statistical literature warns that common methods for comparing groups and studying associations can have relatively poor power compared to more modern robust techniques. Here we illustrate, in secondary data analyses using the USC Well Elderly II study (n = 460, age 60–95, 66% female), that modern robust methods make a substantial difference when analyzing relations between salivary analyte and behavioral data. Analyses that deal with the diurnal pattern of cortisol and the association of the cortisol awakening response with depressive symptoms and physical well-being are reported. Non-significant results become significant when using improved methods for dealing with skewed distributions and outliers. Analytical strategies and tactics that employ modern robust methods have the potential to reduce the probability of both Type I and Type II errors in studies that compare salivary analytes between groups, across time, or examine associations with salivary analyte levels. 相似文献
60.