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1.
Dr. Mads Østergaard Dr. Narendra Kumar Mishra Prof. Dr. Knud J. Jensen 《Chemistry (Weinheim an der Bergstrasse, Germany)》2020,26(38):8341-8357
Insulin is a small protein crucial for regulating the blood glucose level in all animals. Since 1922 it has been used for the treatment of patients with diabetes. Despite consisting of just 51 amino acids, insulin contains 17 of the proteinogenic amino acids, A- and B-chains, three disulfide bridges, and it folds with 3 α-helices and a short β-sheet segment. Insulin associates into dimers and further into hexamers with stabilization by Zn2+ and phenolic ligands. Selective chemical modification of proteins is at the forefront of developments in chemical biology and biopharmaceuticals. Insulin's structure has made it amenable to organic and inorganic chemical reactions. This Review provides a synthetic organic chemistry perspective on this small protein. It gives an overview of key chemical and physico-chemical aspects of the insulin molecule, with a focus on chemoselective reactions. This includes N-acylations at the N-termini or at LysB29 by pH control, introduction of protecting groups on insulin, binding of metal ions, ligands to control the nano-scale assembly of insulin, and more. 相似文献
2.
Tam T. T. N. Nguyen Jesper Østergaard Bente Gammelgaard 《Analytical and bioanalytical chemistry》2015,407(28):8497-8503
3.
Olena Dobrovolska
yvind Strmland
rjan Sele Handegrd Martin Jakubec Morten L. Govasli ge Aleksander Skjevik Nils ge Frystein Knut Teigen
yvind Halskau 《Molecules (Basel, Switzerland)》2021,26(12)
The driving forces and conformational pathways leading to amphitropic protein-membrane binding and in some cases also to protein misfolding and aggregation is the subject of intensive research. In this study, a chimeric polypeptide, A-Cage-C, derived from α-Lactalbumin is investigated with the aim of elucidating conformational changes promoting interaction with bilayers. From previous studies, it is known that A-Cage-C causes membrane leakages associated with the sporadic formation of amorphous aggregates on solid-supported bilayers. Here we express and purify double-labelled A-Cage-C and prepare partially deuterated bicelles as a membrane mimicking system. We investigate A-Cage-C in the presence and absence of these bicelles at non-binding (pH 7.0) and binding (pH 4.5) conditions. Using in silico analyses, NMR, conformational clustering, and Molecular Dynamics, we provide tentative insights into the conformations of bound and unbound A-Cage-C. The conformation of each state is dynamic and samples a large amount of overlapping conformational space. We identify one of the clusters as likely representing the binding conformation and conclude tentatively that the unfolding around the central W23 segment and its reorientation may be necessary for full intercalation at binding conditions (pH 4.5). We also see evidence for an overall elongation of A-Cage-C in the presence of model bilayers. 相似文献
4.
5.
G. G. Pereira W. V. Pinczewski D. Y. C. Chan L. Paterson P. E. Øren 《Transport in Porous Media》1996,24(2):167-201
Drainage displacements in three-phase flow under strongly wetting conditions are completely described by a simple generalisation of well understood two-phase drainage mechanisms. As in two-phase flow, the sequence of throat invasions in three-phase flow is determined by fluid connectivity and threshold capillary pressure for the invading interface. Flow through wetting and intermediate spreading films is important in determining fluid recoveries and the progress of the displacement in three-phase flow. Viscous pressure drops associated with flow through films give rise to multiple filling and emptying of pores. A three-phase, two-dimensional network model based on the pore-scale fluid distributions and displacement mechanisms reported by Øren et al. and which accounts for flow through both wetting and intermediate fluid films is shown to correctly predict all the important characteristics of three-phase flow observed in glass micromodel experiments. 相似文献
6.
The singular value decomposition, SVD, is applied to the linear eigenvalue problem in atomic structure calculations. By comparing with recent calculations of energy levels in neutral Ca, it is shown that the SVD can give quite accurate results and much faster than normal diagonalization techniques, even of the Davidson type. However, the energy levels calculated in this approach are more strongly bound than the real eigenvalues, and this is ascribed to an artefact of the SVD, caused by the use of a discretized continuum in the calculations. This effect can lead to fairly large errors if there is strong CI present. The property of the linear eigenvalue problem that the spectrum is unchanged when a constant is added to the diagonal does not apply to the SVD. This means that it is impossible to solve the problems connected with a discretized continuum simply by shifting the spectrum. 相似文献
7.
Eva C. Sonnenschein Marc Stierhof Stephan Goralczyk Floriane M. Vabre Leonie Pellissier Kine Østnes Hanssen Mercedes de la Cruz Caridad Díaz Peter de Witte Daniëlle Copmans Jeanette Hammer Andersen Espen Hansen Venke Kristoffersen José R. Tormo Rainer Ebel Bruce F. Milne Hai Deng Lone Gram Jioji N. Tabudravu 《Tetrahedron》2017,73(18):2633-2637
A new siderophore containing a 4,5-dihydroimidazole moiety was isolated from Pseudoalteromonas piscicida S2040 together with myxochelins A and B, alteramide A and its cycloaddition product, and bromo- and dibromoalterochromides. The structure of pseudochelin A was established by spectroscopic techniques including 2D NMR and MS/MS fragmentation data. In bioassays selected fractions of the crude extract of S2040 inhibited the opportunistic pathogen Pseudomonas aeruginosa. Pseudochelin A displayed siderophore activity in the chrome azurol S assay at concentrations higher than 50 μM, and showed weak activity against the fungus Aspergillus fumigatus, but did not display antibacterial, anti-inflammatory or anticonvulsant activity. 相似文献
8.
Øystein Stakkestad Anja CV Larsen Anne-Katrine Kvissel Sissel Eikvar Sigurd Ørstavik Bjørn S Skålhegg 《BMC biochemistry》2011,12(1):7
Background
Protein kinase A type I (PKAI) and PKAII are expressed in most of the eukaryotic cells examined. PKA is a major receptor for cAMP and specificity is achieved partly through tissue-dependent expression and subcellular localization of subunits with different biochemical properties. In addition posttranslational modifications help fine tune PKA activity, distribution and interaction in the cell. In spite of this the functional significance of two forms of PKA in one cell has not been fully determined. Here we have tested the ability of PKAI and PKAII formed by expression of the regulatory (R) subunits RIα or RIIα in conjunction with Cα1 or Cβ2 to activate a co-transfected luciferace reporter gene, controlled by the cyclic AMP responsive element-binding protein (CREB) in vivo. 相似文献9.
Ulrik Franzen Lene Jorgensen Claus Larsen Niels H. H. Heegaard Jesper Østergaard 《Electrophoresis》2009,30(15):2711-2719
The potential of using CE frontal analysis (CE‐FA) to study the interactions between a range of charged low molecular weight drug substances and liposomes was evaluated. The liposomes used were net negatively charged and consisted of 2‐oleoyl‐1‐palmitoyl‐sn‐glycero‐3‐phosphocholine and 1,2‐dipalmitoyl‐sn‐glycero‐3‐phosphate monosodium salt in a ratio of 80/20 mol%. Apparent distribution coefficients (Dmem), defined as the molar concentration of drug substance in the membrane phase divided by the molar concentration of drug substance in the aqueous phase, were successfully determined for six positively and eight negatively charged drug substances with log Dmem ranging from 1.35 to 3.63. The extent of liposome–buffer distribution was found to be dependent on the drug concentration. The results obtained with the developed CE‐FA method were in good agreement with results obtained by equilibrium dialysis. Furthermore, the CE‐FA method was faster, less labor intensive and required smaller sample volumes (~50 μL) compared with equilibrium dialysis. Thus, CE‐FA is an efficient and useful tool for the characterization of interactions between liposomes and low molecular weight drug substances. 相似文献
10.
Maja Ludvigsen Morten Østergaard Henrik Vorum Christian Jacobsen Bent Honoré 《BMC biochemistry》2009,10(1):34-11