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981.
Stereoselective Fluorination Alters the Geometry of a Cyclic Peptide: Exploration of Backbone‐Fluorinated Analogues of Unguisin A
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Dr. Xiang‐Guo Hu Dr. Donald S. Thomas Prof. Renate Griffith Dr. Luke Hunter 《Angewandte Chemie (International ed. in English)》2014,53(24):6176-6179
New methods for enhancing the efficiency of peptide cyclization, and for fine‐tuning the conformations of cyclic peptides, are valuable from a drug development perspective. Herein stereoselective fluorination is investigated as a new strategy for achieving these goals. Four vicinal difluorinated analogues of the natural cyclic heptapeptide unguisin A have been efficiently synthesized. The analogues are found to adopt dramatically different secondary structures, controlled by the fluorine stereochemistry. 相似文献
982.
Allenamides as Orthogonal Handles for Selective Modification of Cysteine in Peptides and Proteins
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Ata Abbas Prof. Bengang Xing Prof. Teck‐Peng Loh 《Angewandte Chemie (International ed. in English)》2014,53(29):7491-7494
In this study, a remarkably simple and direct strategy has been successfully developed to selectively label target cysteine residues in fully unprotected peptides and proteins. The strategy is based on the reaction between allenamides and the cysteine thiol, and proceeds swiftly in aqueous medium with excellent selectivity and quantitative conversion, thus forming a stable and irreversible conjugate. The combined simplicity and mildness of the process project allenamide as robust and versatile handles to target cysteines and has potential use in biological systems. Additionally, fluorescent‐labeling studies demonstrated that the installation of a C‐terminal allenamide moiety onto various molecules of interest may supply a new methodology towards the site‐specific labeling of cysteine‐containing proteins. Such a new labeling strategy may thus open a window for its application in the field of life sciences. 相似文献
983.
Peptide Modifications Differentially Alter G Protein‐Coupled Receptor Internalization and Signaling Bias
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Veronika Mäde Stefanie Babilon Dr. Navjeet Jolly Lizzy Wanka Dr. Kathrin Bellmann‐Sickert Dr. Luis E. Diaz Gimenez Dr. Karin Mörl Prof. Dr. Helen M. Cox Prof. Dr. Vsevolod V. Gurevich Prof. Dr. Annette G. Beck‐Sickinger 《Angewandte Chemie (International ed. in English)》2014,53(38):10067-10071
Although G protein‐coupled receptors (GPCRs) are targeted by more clinically used drugs than any other type of protein, their ligand development is particularly challenging. Humans have four neuropeptide Y receptors: hY1R and hY5R are orexigenic, while hY2R and hY4R are anorexigenic, and represent important anti‐obesity drug targets. We show for the first time that PEGylation and lipidation, chemical modifications that prolong the plasma half‐lives of peptides, confer additional benefits. Both modifications enhance pancreatic polypeptide preference for hY2R/hY4R over hY1R/hY5R. Lipidation biases the ligand towards arrestin recruitment and internalization, whereas PEGylation confers the opposite bias. These effects were independent of the cell system and modified residue. We thus provide novel insights into the mode of action of peptide modifications and open innovative venues for generating peptide agonists with extended therapeutic potential. 相似文献
984.
Tao Jiang Dr. Chunfu Xu Dr. Xiaobing Zuo Prof. Vincent P. Conticello 《Angewandte Chemie (International ed. in English)》2014,53(32):8367-8371
A collagen‐mimetic peptide, NSIII, has been designed with three sequential blocks having positive, neutral, and negative charges, respectively. The non‐canonical imino acid, (2S,4S)‐4‐aminoproline (amp), was used to specify the positive charges at the Xaa positions of (Xaa‐Yaa‐Gly) triads in the N‐terminal domain of NSIII. Peptide NSIII underwent self‐assembly from aqueous solution to form a highly homogeneous population of nanosheets. Two‐dimensional crystalline sheets formed in which the length of the peptide defined the height of the sheets. These results contrasted with prior results on a similar multi‐domain collagen‐mimetic polypeptides in which the sheets had highly polydisperse distribution of sizes in the (x/y)‐ and (z)‐dimensions. The structural differences between the two nanosheet assemblies were interpreted in terms of the relative stereoelectronic effects of the different aminoproline derivatives on the local triple helical conformation of the peptides. 相似文献
985.
Lifei Zheng Alessio Marcozzi Dr. Jennifer Y. Gerasimov Prof. Dr. Andreas Herrmann 《Angewandte Chemie (International ed. in English)》2014,53(29):7599-7603
Cyclic peptides containing a disulfide bridge were identified as a simple and versatile coordination sphere for asymmetric catalysis. Upon complexation with Cu2+ ions they catalyze Diels–Alder and Friedel–Crafts reactions with high enantioselectivities of up to 99 % ee and 86 % ee, respectively. Moreover, the peptides ligands were systematically optimized with the assistance of “Alanine Scanning”. This biomolecular design could greatly expand the choice of peptide scaffolds for artificial metallopeptide catalysts. 相似文献
986.
Reversible Supramolecular Assembly at Specific DNA Sites: Nickel‐Promoted Bivalent DNA Binding with Designed Peptide and Bipyridyl–Bis(benzamidine) Components
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987.
Dr. Christofer Lendel Dr. Morten Bjerring Dr. Anatoly Dubnovitsky Robert T. Kelly Dr. Andrei Filippov Prof. Dr. Oleg N. Antzutkin Prof. Dr. Niels Chr. Nielsen Prof. Dr. Torleif Härd 《Angewandte Chemie (International ed. in English)》2014,53(47):12756-12760
Oligomeric and protofibrillar aggregates formed by the amyloid‐β peptide (Aβ) are believed to be involved in the pathology of Alzheimer’s disease. Central to Alzheimer pathology is also the fact that the longer Aβ42 peptide is more prone to aggregation than the more prevalent Aβ40. Detailed structural studies of Aβ oligomers and protofibrils have been impeded by aggregate heterogeneity and instability. We previously engineered a variant of Aβ that forms stable protofibrils and here we use solid‐state NMR spectroscopy and molecular modeling to derive a structural model of these. NMR data are consistent with packing of residues 16 to 42 of Aβ protomers into hexameric barrel‐like oligomers within the protofibril. The core of the oligomers consists of all residues of the central and C‐terminal hydrophobic regions of Aβ, and hairpin loops extend from the core. The model accounts for why Aβ42 forms oligomers and protofibrils more easily than Aβ40. 相似文献
988.
Dr. Wael E. Houssen Andrew F. Bent Dr. Andrew R. McEwan Nathalie Pieiller Dr. Jioji Tabudravu Dr. Jesko Koehnke Greg Mann Rosemary I. Adaba Dr. Louise Thomas Dr. Usama W. Hawas Dr. Huanting Liu Dr. Ulrich Schwarz‐Linek Prof. Margaret C. M. Smith Prof. James H. Naismith Prof. Marcel Jaspars 《Angewandte Chemie (International ed. in English)》2014,53(51):14171-14174
Heterocycle‐containing cyclic peptides are promising scaffolds for the pharmaceutical industry but their chemical synthesis is very challenging. A new universal method has been devised to prepare these compounds by using a set of engineered marine‐derived enzymes and substrates obtained from a family of ribosomally produced and post‐translationally modified peptides called the cyanobactins. The substrate precursor peptide is engineered to have a non‐native protease cleavage site that can be rapidly cleaved. The other enzymes used are heterocyclases that convert Cys or Cys/Ser/Thr into their corresponding azolines. A macrocycle is formed using a macrocyclase enzyme, followed by oxidation of the azolines to azoles with a specific oxidase. The work is exemplified by the production of 17 macrocycles containing 6–9 residues representing 11 out of the 20 canonical amino acids. 相似文献
989.
990.
N‐Methyl‐trimethylacetamide in Thin Films Displays Infrared Spectra of π‐Helices,with Visible Static and Dynamic Growth Phases,and then a β‐Sheet
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Prof. Edward M. Kosower Galina Borz Prof. Israel Goldberg Natalya Ermakov 《Chemphyschem》2014,15(16):3592-3597
The simplest (minimal) peptide model is HCONHCH3. An increase in the π‐helix content with increased substitution in the acyl portion suggested the examination of N‐methyl‐trimethylacetamide) (NMT). NMT displays spectra, in which there is evolution of a set of helices defined by their amide I maxima near 1686 (310), 1655 (first π), and, most importantly, at 1637 cm?1 (π). Expanded thin‐film infrared spectroscopy (XTFIS) shows pauses or slow stages, which are identified as static phases followed by dynamic phases with the incremental gain or loss of a helix turn. In addition, absorbance at 1637 cm?1 suddenly increases at 82.1 s (30 % over 0.3 s), indicating a phase change and crystallization of the π‐helix, along with a coincidental decrease in the absorbance for the first π‐helix. A sharp peak occurs at the maximum of the phase change at 82.5 s, representing a pure NMT π‐helix. The spectra then undergo a decreasing general absorption loss over 150 s, with the π‐helix evolving further to an antiparallel β‐sheet fragment. The spectral quality arises from the immobilization of polar molecules on polar surfaces. The crystal structure is that of an antiparallel β‐sheet. 相似文献