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991.
Spontaneous Reconstitution of Functional Transmembrane Proteins During Bioorthogonal Phospholipid Membrane Synthesis 下载免费PDF全文
Christian M. Cole Dr. Roberto J. Brea Young Hun Kim Michael D. Hardy Prof. Jerry Yang Prof. Neal K. Devaraj 《Angewandte Chemie (International ed. in English)》2015,54(43):12738-12742
Transmembrane proteins are critical for signaling, transport, and metabolism, yet their reconstitution in synthetic membranes is often challenging. Non‐enzymatic and chemoselective methods to generate phospholipid membranes in situ would be powerful tools for the incorporation of membrane proteins. Herein, the spontaneous reconstitution of functional integral membrane proteins during the de novo synthesis of biomimetic phospholipid bilayers is described. The approach takes advantage of bioorthogonal coupling reactions to generate proteoliposomes from micelle‐solubilized proteins. This method was successfully used to reconstitute three different transmembrane proteins into synthetic membranes. This is the first example of the use of non‐enzymatic chemical synthesis of phospholipids to prepare proteoliposomes. 相似文献
992.
Structural Insights into the Incorporation of the Mo Cofactor into Sulfite Oxidase from Site‐Directed Spin Labeling 下载免费PDF全文
Dr. Aaron Hahn Christopher Engelhard Dr. Stefan Reschke Dr. Christian Teutloff Prof. Dr. Robert Bittl Prof. Dr. Silke Leimkühler Prof. Dr. Thomas Risse 《Angewandte Chemie (International ed. in English)》2015,54(40):11865-11869
Mononuclear molybdoenzymes catalyze a broad range of redox reactions and are highly conserved in all kingdoms of life. This study addresses the question of how the Mo cofactor (Moco) is incorporated into the apo form of human sulfite oxidase (hSO) by using site‐directed spin labeling to determine intramolecular distances in the nanometer range. Comparative measurements of the holo and apo forms of hSO enabled the localization of the corresponding structural changes, which are localized to a short loop (residues 263–273) of the Moco‐containing domain. A flap‐like movement of the loop provides access to the Moco binding‐pocket in the apo form of the protein and explains the earlier studies on the in vitro reconstitution of apo‐hSO with Moco. Remarkably, the loop motif can be found in a variety of structurally similar molybdoenzymes among various organisms, thus suggesting a common mechanism of Moco incorporation. 相似文献
993.
Olivia Schimming Dr. Victoria L. Challinor Dr. Nicholas J. Tobias Dr. Hélène Adihou Peter Grün Laura Pöschel Dr. Christian Richter Prof. Dr. Harald Schwalbe Prof. Dr. Helge B. Bode 《Angewandte Chemie (International ed. in English)》2015,54(43):12702-12705
Pyrrolizidine alkaloids (PAs) are widespread plant natural products with potent toxicity and bioactivity. Herein, the identification of bacterial PAs from entomopathogenic bacteria using differential analysis by 2D NMR spectroscopy (DANS) and mass spectrometry is described. Their biosynthesis was elucidated to involve a non‐ribosomal peptide synthetase. The occurrence of these biosynthesis gene clusters in Gram‐negative and Gram‐positive bacteria indicates an important biological function in bacteria. 相似文献
994.
Nannocystin A: an Elongation Factor 1 Inhibitor from Myxobacteria with Differential Anti‐Cancer Properties 下载免费PDF全文
Philipp Krastel Silvio Roggo Markus Schirle Nathan T. Ross Francesca Perruccio Peter Aspesi Jr. Thomas Aust Kathrin Buntin David Estoppey Brigitta Liechty Felipa Mapa Klaus Memmert Howard Miller Xuewen Pan Ralph Riedl Christian Thibaut Jason Thomas Trixie Wagner Eric Weber Xiaobing Xie Esther K. Schmitt Dr. Dominic Hoepfner 《Angewandte Chemie (International ed. in English)》2015,54(35):10149-10154
Cultivation of myxobacteria of the Nannocystis genus led to the isolation and structure elucidation of a class of novel cyclic lactone inhibitors of elongation factor 1. Whole genome sequence analysis and annotation enabled identification of the putative biosynthetic cluster and synthesis process. In biological assays the compounds displayed anti‐fungal and cytotoxic activity. Combined genetic and proteomic approaches identified the eukaryotic translation elongation factor 1α (EF‐1α) as the primary target for this compound class. Nannocystin A ( 1 ) displayed differential activity across various cancer cell lines and EEF1A1 expression levels appear to be the main differentiating factor. Biochemical and genetic evidence support an overlapping binding site of 1 with the anti‐cancer compound didemnin B on EF‐1α. This myxobacterial chemotype thus offers an interesting starting point for further investigations of the potential of therapeutics targeting elongation factor 1. 相似文献
995.
A Filled‐Honeycomb‐Structured Crystal Formed by Self‐Assembly of a Janus Polyoxometalate–Silsesquioxane (POM–POSS) Co‐Cluster 下载免费PDF全文
Chi Ma Han Wu Zi‐Han Huang Dr. Ruo‐Hai Guo Dr. Min‐Biao Hu Dr. Christian Kübel Prof. Dr. Li‐Tang Yan Prof. Dr. Wei Wang 《Angewandte Chemie (International ed. in English)》2015,54(52):15699-15704
Clusters with diverse structures and functions have been used to create novel cluster‐assembled materials (CAMs). Understanding their self‐assembly process is a prerequisite to optimize their structure and function. Herein, two kinds of unlike organo‐functionalized inorganic clusters are covalently linked by a short organic tether to form a dumbbell‐shaped Janus co‐cluster. In a mixed solvent of acetonitrile and water, it self‐assembles into a crystal with a honeycomb superstructure constructed by hexagonal close‐packed cylinders of the smaller cluster and an orderly arranged framework of the larger cluster. Reconstruction of these structural features via coarse‐grained molecular simulations demonstrates that the cluster crystallization and the nanoscale phase separation between the two incompatible clusters synergistically result in the unique nano‐architecture. Overall, this work opens up new opportunities for generating novel CAMs for advanced future applications. 相似文献
996.
Dr. Lech‐Gustav Milroy Dr. Maria Bartel Dr. Morkos A. Henen Dr. Seppe Leysen Joris M. C. Adriaans Prof. Dr. Luc Brunsveld Dr. Isabelle Landrieu Dr. Christian Ottmann 《Angewandte Chemie (International ed. in English)》2015,54(52):15720-15724
The discovery of novel protein–protein interaction (PPI) modulators represents one of the great molecular challenges of the modern era. PPIs can be modulated by either inhibitor or stabilizer compounds, which target different though proximal regions of the protein interface. In principle, protein–stabilizer complexes can guide the design of PPI inhibitors (and vice versa). In the present work, we combine X‐ray crystallographic data from both stabilizer and inhibitor co‐crystal complexes of the adapter protein 14‐3‐3 to characterize, down to the atomic scale, inhibitors of the 14‐3‐3/Tau PPI, a potential drug target to treat Alzheimer’s disease. The most potent compound notably inhibited the binding of phosphorylated full‐length Tau to 14‐3‐3 according to NMR spectroscopy studies. Our work sets a precedent for the rational design of PPI inhibitors guided by PPI stabilizer–protein complexes while potentially enabling access to new synthetically tractable stabilizers of 14‐3‐3 and other PPIs. 相似文献
997.
CH Oxidation of Ingenanes Enables Potent and Selective Protein Kinase C Isoform Activation 下载免费PDF全文
Dr. Yehua Jin Dr. Chien‐Hung Yeh Dr. Christian A. Kuttruff Dr. Lars Jørgensen Dr. Georg Dünstl Dr. Jakob Felding Dr. Swaminathan R. Natarajan Prof. Dr. Phil S. Baran 《Angewandte Chemie (International ed. in English)》2015,54(47):14044-14048
Ingenol derivatives with varying degrees of oxidation were prepared by two‐phase terpene synthesis. This strategy has allowed access to analogues that cannot be prepared by semisynthesis from natural ingenol. Complex ingenanes resulting from divergent C? H oxidation of a common intermediate were found to interact with protein kinase C in a manner that correlates well with the oxidation state of the ingenane core. Even though previous work on ingenanes has suggested a strong correlation between potential to activate PKCδ and induction of neutrophil oxidative burst, the current study shows that the potential to activate PKCβII is of key importance while interaction with PKCδ is dispensable. Thus, key modifications of the ingenane core allowed PKC isoform selectivity wherein PKCδ‐driven activation of keratinocytes is strongly reduced or even absent while PKCβII‐driven activation of neutrophils is retained. 相似文献
998.
Cover Picture: Metal‐Free Addition/Head‐to‐Tail Polymerization of Transient Phosphinoboranes,RPH‐BH2: A Route to Poly(alkylphosphinoboranes) (Angew. Chem. Int. Ed. 46/2015) 下载免费PDF全文
999.
Covalent Attachment of Cyclic TAT Peptides to GFP Results in Protein Delivery into Live Cells with Immediate Bioavailability 下载免费PDF全文
Dr. Francesco Natale Nina Bohlke Prof. Nediljko Budisa Prof. M. Cristina Cardoso Prof. Christian P. R. Hackenberger 《Angewandte Chemie (International ed. in English)》2015,54(6):1950-1953
The delivery of free molecules into the cytoplasm and nucleus by using arginine‐rich cell‐penetrating peptides (CPPs) has been limited to small cargoes, while large cargoes such as proteins are taken up and trapped in endocytic vesicles. Based on recent work, in which we showed that the transduction efficiency of arginine‐rich CPPs can be greatly enhanced by cyclization, the aim was to use cyclic CPPs to transport full‐length proteins, in this study green fluorescent protein (GFP), into the cytosol of living cells. Cyclic and linear CPP–GFP conjugates were obtained by using azido‐functionalized CPPs and an alkyne‐functionalized GFP. Our findings reveal that the cyclic‐CPP–GFP conjugates are internalized into live cells with immediate bioavailability in the cytosol and the nucleus, whereas linear CPP analogues do not confer GFP transduction. This technology expands the application of cyclic CPPs to the efficient transport of functional full‐length proteins into live cells. 相似文献
1000.
Christian P. Sindlinger Sebastian Weiß Dr. Hartmut Schubert Prof. Dr. Lars Wesemann 《Angewandte Chemie (International ed. in English)》2015,54(13):4087-4091
NHC adducts of the stannylene Trip2Sn (Trip=2,4,6‐triisopropylphenyl) were reacted with zero‐valent Ni, Pd, and Pt precursor complexes to cleanly yield the respective metal complexes featuring a three‐membered ring moiety Sn‐Sn‐M along with carbene transfer onto the metal and complete substitution of the starting ligands. Thus the easily accessible NHC adducts to stannylenes are shown to be valuable precursors for transition‐metal complexes with an unexpected Sn? Sn bond. The complexes have been studied by X‐ray diffraction and NMR spectroscopy as well as DFT calculations. The compounds featuring the structural motif of a distannametallacycle comprised of a [(NHC)2M0] fragment and Sn2Trip4 represent rare higher congeners of the well‐known olefin complexes. DFT calculations indicate the presence of a π‐type Sn–Sn interaction in these first examples for acyclic distannenes symmetrically coordinating to a zero‐valent transition metal. 相似文献