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991.
Inside Cover: Breakable Hybrid Organosilica Nanocapsules for Protein Delivery (Angew. Chem. Int. Ed. 10/2016) 下载免费PDF全文
992.
Engineering a Chemical Switch into the Light‐driven Proton Pump Proteorhodopsin by Cysteine Mutagenesis and Thiol Modification 下载免费PDF全文
Dr. Daniel Harder Stephan Hirschi Zöhre Ucurum Roland Goers Prof. Dr. Wolfgang Meier Prof. Dr. Daniel J. Müller Prof. Dr. Dimitrios Fotiadis 《Angewandte Chemie (International ed. in English)》2016,55(31):8846-8849
For applications in synthetic biology, for example, the bottom‐up assembly of biomolecular nanofactories, modules of specific and controllable functionalities are essential. Of fundamental importance in such systems are energizing modules, which are able to establish an electrochemical gradient across a vesicular membrane as an energy source for powering other modules. Light‐driven proton pumps like proteorhodopsin (PR) are excellent candidates for efficient energy conversion. We have extended the versatility of PR by implementing an on/off switch based on reversible chemical modification of a site‐specifically introduced cysteine residue. The position of this cysteine residue in PR was identified by structure‐based cysteine mutagenesis combined with a proton‐pumping assay using E. coli cells overexpressing PR and PR proteoliposomes. The identified PR mutant represents the first light‐driven proton pump that can be chemically switched on/off depending on the requirements of the molecular system. 相似文献
993.
Radiation Damage and Racemic Protein Crystallography Reveal the Unique Structure of the GASA/Snakin Protein Superfamily 下载免费PDF全文
Ho Yeung Dr. Christopher J. Squire Yuliana Yosaatmadja Dr. Santosh Panjikar Gemma López Prof. Dr. Antonio Molina Prof. Dr. Edward N. Baker Dr. Paul W. R. Harris Prof. Dr. Margaret A. Brimble 《Angewandte Chemie (International ed. in English)》2016,55(28):7930-7933
Proteins from the GASA/snakin superfamily are common in plant proteomes and have diverse functions, including hormonal crosstalk, development, and defense. One 63‐residue member of this family, snakin‐1, an antimicrobial protein from potatoes, has previously been chemically synthesized in a fully active form. Herein the 1.5 Å structure of snakin‐1, determined by a novel combination of racemic protein crystallization and radiation‐damage‐induced phasing (RIP), is reported. Racemic crystals of snakin‐1 and quasi‐racemic crystals incorporating an unnatural 4‐iodophenylalanine residue were prepared from chemically synthesized d ‐ and l ‐proteins. Breakage of the C?I bonds in the quasi‐racemic crystals facilitated structure determination by RIP. The crystal structure reveals a unique protein fold with six disulfide crosslinks, presenting a distinct electrostatic surface that may target the protein to microbial cell surfaces. 相似文献
994.
Efficient Palladium‐Assisted One‐Pot Deprotection of (Acetamidomethyl)Cysteine Following Native Chemical Ligation and/or Desulfurization To Expedite Chemical Protein Synthesis 下载免费PDF全文
Dr. Suman Kumar Maity Muhammad Jbara Shay Laps Prof. Ashraf Brik 《Angewandte Chemie (International ed. in English)》2016,55(28):8108-8112
The acetamidomethyl (Acm) moiety is a widely used cysteine protecting group for the chemical synthesis and semisynthesis of peptide and proteins. However, its removal is not straightforward and requires harsh reaction conditions and additional purification steps before and after the removal step, which extends the synthetic process and reduces the overall yield. To overcome these shortcomings, a method for rapid and efficient Acm removal using PdII complexes in aqueous medium is reported. We show, for the first time, the assembly of three peptide fragments in a one‐pot fashion by native chemical ligation where the Acm moiety was used to protect the N‐terminal Cys of the middle fragment. Importantly, an efficient synthesis of the ubiquitin‐like protein UBL‐5, which contains two native Cys residues, was accomplished through the one‐pot operation of three key steps, namely ligation, desulfurization, and Acm deprotection, highlighting the great utility of the new approach in protein synthesis. 相似文献
995.
996.
Identification of HcgC as a SAM‐Dependent Pyridinol Methyltransferase in [Fe]‐Hydrogenase Cofactor Biosynthesis 下载免费PDF全文
Dr. Takashi Fujishiro Liping Bai Dr. Tao Xu Dr. Xiulan Xie Dr. Michael Schick Jörg Kahnt Prof. Dr. Michael Rother Prof. Dr. Xile Hu Dr. Ulrich Ermler Dr. Seigo Shima 《Angewandte Chemie (International ed. in English)》2016,55(33):9648-9651
Previous retrosynthetic and isotope‐labeling studies have indicated that biosynthesis of the iron guanylylpyridinol (FeGP) cofactor of [Fe]‐hydrogenase requires a methyltransferase. This hypothetical enzyme covalently attaches the methyl group at the 3‐position of the pyridinol ring. We describe the identification of HcgC, a gene product of the hcgA‐G cluster responsible for FeGP cofactor biosynthesis. It acts as an S‐adenosylmethionine (SAM)‐dependent methyltransferase, based on the crystal structures of HcgC and the HcgC/SAM and HcgC/S‐adenosylhomocysteine (SAH) complexes. The pyridinol substrate, 6‐carboxymethyl‐5‐methyl‐4‐hydroxy‐2‐pyridinol, was predicted based on properties of the conserved binding pocket and substrate docking simulations. For verification, the assumed substrate was synthesized and used in a kinetic assay. Mass spectrometry and NMR analysis revealed 6‐carboxymethyl‐3,5‐dimethyl‐4‐hydroxy‐2‐pyridinol as the reaction product, which confirmed the function of HcgC. 相似文献
997.
A Modular Method for the High‐Yield Synthesis of Site‐Specific Protein–Polymer Therapeutics 下载免费PDF全文
Dr. Xinghai Li Prof. Ashutosh Chilkoti 《Angewandte Chemie (International ed. in English)》2016,55(35):10296-10300
A versatile method is described to engineer precisely defined protein/peptide–polymer therapeutics by a modular approach that consists of three steps: 1) fusion of a protein/peptide of interest with an elastin‐like polypeptide that enables facile purification and high yields; 2) installation of a clickable group at the C terminus of the recombinant protein/peptide with almost complete conversion by enzyme‐mediated ligation; and 3) attachment of a polymer by a click reaction with near‐quantitative conversion. We demonstrate that this modular approach is applicable to various protein/peptide drugs and used it to conjugate them to structurally diverse water‐soluble polymers that prolong the plasma circulation duration of these proteins. The protein/peptide–polymer conjugates exhibited significantly improved pharmacokinetics and therapeutic effects over the native protein/peptide upon administration to mice. The studies reported here provide a facile method for the synthesis of protein/peptide–polymer conjugates for therapeutic use and other applications. 相似文献
998.
Bioorthogonal Probes for the Study of MDM2‐p53 Inhibitors in Cells and Development of High‐Content Screening Assays for Drug Discovery 下载免费PDF全文
Pier Luca D'Alessandro Nicole Buschmann Markus Kaufmann Dr. Pascal Furet Frederic Baysang Reto Brunner Dr. Andreas Marzinzik Dr. Thomas Vorherr Dr. Therese‐Marie Stachyra Dr. Johannes Ottl Dr. Dimitrios E. Lizos Dr. Amanda Cobos‐Correa 《Angewandte Chemie (International ed. in English)》2016,55(52):16026-16030
To study the behavior of MDM2‐p53 inhibitors in a disease‐relevant cellular model, we have developed and validated a set of bioorthogonal probes that can be fluorescently labeled in cells and used in high‐content screening assays. By using automated image analysis with single‐cell resolution, we could visualize the intracellular target binding of compounds by co‐localization and quantify target upregulation upon MDM2‐p53 inhibition in an osteosarcoma model. Additionally, we developed a high‐throughput assay to quantify target occupancy of non‐tagged MDM2‐p53 inhibitors by competition and to identify novel chemical matter. This approach could be expanded to other targets for lead discovery applications. 相似文献
999.
Conversion of the Native 24‐mer Ferritin Nanocage into Its Non‐Native 16‐mer Analogue by Insertion of Extra Amino Acid Residues 下载免费PDF全文
Shengli Zhang Jiachen Zang Wenming Wang Hai Chen Xiaorong Zhang Fudi Wang Prof. Hongfei Wang Prof. Guanghua Zhao 《Angewandte Chemie (International ed. in English)》2016,55(52):16064-16070
Protein assemblies with high symmetry are widely distributed in nature. Most efforts so far have focused on repurposing these protein assemblies, a strategy that is ultimately limited by the structures available. To overcome this limitation, methods for fabricating novel self‐assembling proteins have received intensive interest. Herein, by reengineering the key subunit interfaces of native 24‐mer protein cage with octahedral symmetry through amino acid residues insertion, we fabricated a 16‐mer lenticular nanocage whose structure is unique among all known protein cages. This newly non‐native protein can be used for encapsulation of bioactive compounds and exhibits high uptake efficiency by cancer cells. More importantly, the above strategy could be applied to other naturally occurring protein assemblies with high symmetry, leading to the generation of new proteins with unexplored functions. 相似文献
1000.
Use of Lanthanide‐Containing Polyoxometalates to Sensitise the Emission of Fluorescent Labelled Serum Albumin 下载免费PDF全文
Dr. A. Sheila Holmes‐Smith Jacob Crisp Dr. Firasat Hussain Prof. Dr. Greta R. Patzke Dr. Graham Hungerford 《Chemphyschem》2016,17(3):418-424
Monitoring the interaction of biomolecules is important, and the use of energy transfer is a principal technique in elucidating nanoscale interactions. Lanthanide compounds are promising luminescent probes for biological samples as their emission is longer‐lived than any native autofluorescence. Polyoxometalates (POMs) are interesting structural motifs to incorporate lanthanides, offering low toxicity and a size pertinent for biological applications. Here, we employ iso‐structured POMs containing either terbium or europium and assess their interaction with serum albumin by sensitisation of a fluorescent tag on the protein via LRET (luminescence resonance energy transfer) by exciting the lanthanide. Time‐resolved measurements showed energy transfer with an efficiency of over 90 % for the POM–protein systems. The Tb–POM results were relatively straightforward, while those with the iso‐structured Eu–POM were complicated by the effect of protein shielding from the aqueous environment. 相似文献