排序方式: 共有34条查询结果,搜索用时 15 毫秒
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Singh Y Sharpe PC Hoang HN Lucke AJ McDowall AW Bottomley SP Fairlie DP 《Chemistry (Weinheim an der Bergstrasse, Germany)》2011,17(1):151-160
Transformation of proteins and peptides to fibrillar aggregates rich in β sheets underlies many diseases, but mechanistic details of these structural transitions are poorly understood. To simulate aggregation, four equivalents of a water‐soluble, α‐helical (65 %) amphipathic peptide (AEQLLQEAEQLLQEL) were assembled in parallel on an oxazole‐containing macrocyclic scaffold. The resulting 4α‐helix bundle is monomeric and even more α helical (85 %), but it is also unstable at pH 4 and undergoes concentration‐dependent conversion to β‐sheet aggregates and amyloid fibrils. Fibrils twist and grow with time, remaining flexible like rope (>1 μm long, 5–50 nm wide) with multiple strings (2 nm), before ageing to matted fibers. At pH 7 the fibrils revert back to soluble monomeric 4α‐helix bundles. During α→β folding we were able to detect soluble 310 helices in solution by using 2D‐NMR, CD and FTIR spectroscopy. This intermediate satisfies the need for peptide elongation, from the compressed α helix to the fully extended β strand/sheet, and is driven here by 310‐helix aggregation triggered in this case by template‐promoted helical bundling and by hydrogen‐bonding glutamic acid side chains. A mechanism involving α?α4?(310)4?(310)n?(β)n?m(β)n equilibria is plausible for this peptide and also for peptides lacking hydrogen‐bonding side chains, with unfavourable equilibria slowing the α→β conversion. 相似文献
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Dudzinski KM Brown SJ Lammers M Lucke K Mann DA Simard P Wall CC Rasmussen MH Magnúsdóttir EE Tougaard J Eriksen N 《The Journal of the Acoustical Society of America》2011,129(1):436-448
Deployment of any type of measuring device into the ocean, whether to shallow or deeper depths, is accompanied by the hope that this equipment and associated data will be recovered. The ocean is harsh on gear. Salt water corrodes. Currents, tides, surge, storms, and winds collaborate to increase the severity of the conditions that monitoring devices will endure. All ocean-related research has encountered the situations described in this paper. In collating the details of various deployment and recovery scenarios related to stationary passive acoustic monitoring use in the ocean, it is the intent of this paper to share trouble-shooting successes and failures to guide future work with this gear to monitor marine mammal, fish, and ambient (biologic and anthropogenic) sounds in the ocean-in both coastal and open waters. 相似文献
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Daniel S. Nielsen Dr. Huy N. Hoang Dr. Rink‐Jan Lohman Dr. Timothy A. Hill Dr. Andrew J. Lucke Prof. Dr. David J. Craik Dr. David J. Edmonds Dr. David A. Griffith Charles J. Rotter Dr. Roger B. Ruggeri Dr. David A. Price Dr. Spiros Liras Prof. Dr. David P. Fairlie 《Angewandte Chemie (International ed. in English)》2014,53(45):12059-12063
The use of peptides in medicine is limited by low membrane permeability, metabolic instability, high clearance, and negligible oral bioavailability. The prediction of oral bioavailability of drugs relies on physicochemical properties that favor passive permeability and oxidative metabolic stability, but these may not be useful for peptides. Here we investigate effects of heterocyclic constraints, intramolecular hydrogen bonds, and side chains on the oral bioavailability of cyclic heptapeptides. NMR‐derived structures, amide H–D exchange rates, and temperature‐dependent chemical shifts showed that the combination of rigidification, stronger hydrogen bonds, and solvent shielding by branched side chains enhances the oral bioavailability of cyclic heptapeptides in rats without the need for N‐methylation. 相似文献
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D. Acel A. Hahn M. Richter-Quittner J. K. Parnas R. Wagner R. Wodon O. Folin H. Bierry L. Moquet C. M. Wilhelmj E. Ponder W. Autenrieth H. Taege P. Cristol F. Utz G. E. Youngburg J. Munich L. Michaelis M. Maeda F. Fonseca Pincussen A. T. Merril H. Lucke J. C. Bock M. Gilbert 《Analytical and bioanalytical chemistry》1926,69(7-8):314-320
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Die einfachste Möglichkeit der autoradiographischen Abbildung mehrerer Radionuklide in einer Probe besteht bei genügend unterschiedlichen Halbwertszeiten. Ein Rechenbeispiel zeigt, daβ auch bei günstigen Abstufungen der Halbwertszeiten und spezifischen Aktivitaäten für praktishche Anwendungen nicht mehr als drei Radionuklide ohne gegenseitige Störung nacheinander autoradiographiert werden können. Bei der Unterschung von Silikatbaustoffproben wurde nach der Neutronenaktivierung erst die Verteilung der 24Nu und danach die des 15Ca abgebildet. 相似文献
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