共查询到20条相似文献,搜索用时 15 毫秒
1.
Cover Picture: Diphenylacetylene‐Linked Peptide Strands Induce Bidirectional β‐Sheet Formation (Angew. Chem. Int. Ed. 14/2014) 下载免费PDF全文
Dr. Hannah Lingard Jeongmin T. Han Dr. Amber L. Thompson Dr. Ivanhoe K. H. Leung Dr. Richard T. W. Scott Dr. Sam Thompson Prof. Andrew D. Hamilton 《Angewandte Chemie (International ed. in English)》2014,53(14):3521-3521
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Jonathan E. Ross Dr. Peter C. Knipe Dr. Sam Thompson Prof. Dr. Andrew D. Hamilton 《Chemistry (Weinheim an der Bergstrasse, Germany)》2015,21(39):13518-13521
Functionalized diphenylalkynes provide a template for the presentation of protein‐like surfaces composed of multistrand β‐sheets. The conformational properties of three‐, four‐, and seven‐stranded systems have been investigated in the solid‐ and solution‐state. This class of molecule may be suitable for the mediation of therapeutically relevant protein–protein interactions. 相似文献
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Elizabeth A. German Jonathan E. Ross Dr. Peter C. Knipe Michaela F. Don Dr. Sam Thompson Prof. Dr. Andrew D. Hamilton 《Angewandte Chemie (International ed. in English)》2015,54(9):2649-2652
Many therapeutically relevant protein–protein interactions contain hot‐spot regions on secondary structural elements, which contribute disproportionately to binding enthalpy. Mimicry of such α‐helical regions has met with considerable success, however the analogous approach for the β‐strand has received less attention. Presented herein is a foldamer for strand mimicry in which dipolar repulsion is a central determinant of conformation. Computation as well as solution‐ and solid‐phase data are consistent with an ensemble weighted almost exclusively in favor of the desired conformation. 相似文献
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Atsushi Suenaga Dr. Tetsu Narumi Dr. Noriyuki Futatsugi Dr. Ryoko Yanai Yousuke Ohno Dr. Noriaki Okimoto Dr. Makoto Taiji Dr. 《化学:亚洲杂志》2007,2(5):591-598
Short peptides that fold into β‐hairpins are ideal model systems for investigating the mechanism of protein folding because their folding process shows dynamics typical of proteins. We performed folding, unfolding, and refolding molecular dynamics simulations (total of 2.7 μs) of the 10‐residue β‐hairpin peptide chignolin, which is the smallest β‐hairpin structure known to be stable in solution. Our results revealed the folding mechanism of chignolin, which comprises three steps. First, the folding begins with hydrophobic assembly. It brings the main chain together; subsequently, a nascent turn structure is formed. The second step is the conversion of the nascent turn into a tight turn structure along with interconversion of the hydrophobic packing and interstrand hydrogen bonds. Finally, the formation of the hydrogen‐bond network and the complete hydrophobic core as well as the arrangement of side‐chain–side‐chain interactions occur at approximately the same time. This three‐step mechanism appropriately interprets the folding process as involving a combination of previous inconsistent explanations of the folding mechanism of the β‐hairpin, that the first event of the folding is formation of hydrogen bonds and the second is that of the hydrophobic core, or vice versa. 相似文献
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Induced Folding of Protein‐Sized Foldameric β‐Sandwich Models with Core β‐Amino Acid Residues 下载免费PDF全文
Gábor Olajos Dr. Anasztázia Hetényi Dr. Edit Wéber Lukács J. Németh Dr. Zsolt Szakonyi Prof. Dr. Ferenc Fülöp Prof. Dr. Tamás A. Martinek 《Chemistry (Weinheim an der Bergstrasse, Germany)》2015,21(16):6173-6180
The mimicry of protein‐sized β‐sheet structures with unnatural peptidic sequences (foldamers) is a considerable challenge. In this work, the de novo designed betabellin‐14 β‐sheet has been used as a template, and α→β residue mutations were carried out in the hydrophobic core (positions 12 and 19). β‐Residues with diverse structural properties were utilized: Homologous β3‐amino acids, (1R,2S)‐2‐aminocyclopentanecarboxylic acid (ACPC), (1R,2S)‐2‐aminocyclohexanecarboxylic acid (ACHC), (1R,2S)‐2‐aminocyclohex‐3‐enecarboxylic acid (ACEC), and (1S,2S,3R,5S)‐2‐amino‐6,6‐dimethylbicyclo[3.1.1]heptane‐3‐carboxylic acid (ABHC). Six α/β‐peptidic chains were constructed in both monomeric and disulfide‐linked dimeric forms. Structural studies based on circular dichroism spectroscopy, the analysis of NMR chemical shifts, and molecular dynamics simulations revealed that dimerization induced β‐sheet formation in the 64‐residue foldameric systems. Core replacement with (1R,2S)‐ACHC was found to be unique among the β‐amino acid building blocks studied because it was simultaneously able to maintain the interstrand hydrogen‐bonding network and to fit sterically into the hydrophobic interior of the β‐sandwich. The novel β‐sandwich model containing 25 % unnatural building blocks afforded protein‐like thermal denaturation behavior. 相似文献
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Valeria Castelletto Dr. Ian W. Hamley Prof. Rohan A. Hule Dr. Darrin Pochan Prof. 《Angewandte Chemie (International ed. in English)》2009,48(13):2317-2320
An addition to the family : The introduction of β‐amino acid residues into a modified amyloid β peptide fragment resulted in well‐defined helical nanoribbons (see cryo‐TEM image) comprising β strands mainly oriented perpendicular to the ribbon axis. The nanoribbons order into a flow‐aligning nematic phase at higher concentration. The β‐strand nanoribbon structure is an addition to the known set of secondary structures adopted by β‐peptides.
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《Chemistry (Weinheim an der Bergstrasse, Germany)》2006,12(2):403-412
Peptide secondary structure mimetics are important tools in medicinal chemistry, as they provide analogues of endogenous peptides with new physicochemical and pharmacological properties. The development, synthesis, photochemical investigation, and conformational analysis of a stilbene‐type β‐hairpin mimetic capable of light‐triggered conformational changes have been achieved. In addition to standard spectroscopic techniques (nuclear Overhauser effects, amide temperature coefficients, circular dichroism spectroscopy), the applicability of self‐diffusion measurements (longitudinal eddy current delay pulsed‐field gradient spin echo (LED‐PGSE) NMR technique) in conformational studies of oligopeptides is demonstrated. The title compound shows photoisomerization of the stilbene chromophore, resulting in a change in solution conformation between an unfolded structure and a folded β‐hairpin. 相似文献
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Back Cover: Induced Folding of Protein‐Sized Foldameric β‐Sandwich Models with Core β‐Amino Acid Residues (Chem. Eur. J. 16/2015) 下载免费PDF全文
Gábor Olajos Dr. Anasztázia Hetényi Dr. Edit Wéber Lukács J. Németh Dr. Zsolt Szakonyi Prof. Dr. Ferenc Fülöp Prof. Dr. Tamás A. Martinek 《Chemistry (Weinheim an der Bergstrasse, Germany)》2015,21(16):6304-6304
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Yong‐beom Lim Dr. Kyung‐Soo Moon Myongsoo Lee Prof. 《Angewandte Chemie (International ed. in English)》2009,48(9):1601-1605
Protein roll call : Peptide‐based building blocks, in which both an α‐helix‐forming segment and a β‐sheet segment are located within a single macrocyclic structure, self‐assemble into α‐helix‐decorated artificial proteins. This approach provides a starting point for developing artificial proteins that can modulate α‐helix‐mediated interactions occurring in a multivalent fashion.
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Krishnayan Basuroy Appavu Rajagopal Dr. Srinivasarao Raghothama Prof. Narayanaswamy Shamala Prof. Padmanabhan Balaram 《化学:亚洲杂志》2012,7(7):1671-1678
The effect of gem‐dialkyl substituents on the backbone conformations of β‐amino acid residues in peptides has been investigated by using four model peptides: Boc‐Xxx‐β2,2Ac6c(1‐aminomethylcyclohexanecarboxylic acid)‐NHMe (Xxx=Leu ( 1 ), Phe ( 2 ); Boc=tert‐butyloxycarbonyl) and Boc‐Xxx‐β3,3Ac6c(1‐aminocyclohexaneacetic acid)‐NHMe (Xxx=Leu ( 3 ), Phe ( 4 )). Tetrasubstituted carbon atoms restrict the ranges of stereochemically allowed conformations about flanking single bonds. The crystal structure of Boc‐Leu‐β2,2Ac6c‐NHMe ( 1 ) established a C11 hydrogen‐bonded turn in the αβ‐hybrid sequence. The observed torsion angles (α(?≈?60°, ψ≈?30°), β(?≈?90°, θ≈60°, ψ≈?90°)) corresponded to a C11 helical turn, which was a backbone‐expanded analogue of the type III β turn in αα sequences. The crystal structure of the peptide Boc‐Phe‐β3,3Ac6c‐NHMe ( 4 ) established a C11 hydrogen‐bonded turn with distinctly different backbone torsion angles (α(?≈?60°, ψ≈120°), β(?≈60°, θ≈60°, ψ≈?60°)), which corresponded to a backbone‐expanded analogue of the type II β turn observed in αα sequences. In peptide 4 , the two molecules in the asymmetric unit adopted backbone torsion angles of opposite signs. In one of the molecules, the Phe residue adopted an unfavorable backbone conformation, with the energetic penalty being offset by a favorable aromatic interaction between proximal molecules in the crystal. NMR spectroscopy studies provided evidence for the maintenance of folded structures in solution in these αβ‐hybrid sequences. 相似文献
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Genetically engineered spider silk‐like block copolymers were studied to determine the influence of polyalanine domain size on secondary structure. The role of polyalanine block distribution on β‐sheet formation was explored using FT‐IR and WAXS. The number of polyalanine blocks had a direct effect on the formation of crystalline β‐sheets, reflected in the change in crystallinity index as the blocks of polyalanines increased. WAXS analysis confirmed the crystalline nature of the sample with the largest number of polyalanine blocks. This approach provides a platform for further exploration of the role of specific amino acid chemistries in regulating the assembly of β‐sheet secondary structures, leading to options to regulate material properties through manipulation of this key component in spider silks.
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Dr. Sara Pellegrino Dr. Alessandro Contini Prof. Francesca Clerici Dr. Alessandro Gori Donatella Nava Prof. Maria Luisa Gelmi 《Chemistry (Weinheim an der Bergstrasse, Germany)》2012,18(28):8705-8715
A very efficient synthesis of orthogonally protected 1H‐azepine‐4‐amino‐4‐carboxylic acid, abbreviated as Azn, a conformationally restricted analogue of ornithine, was realized. It was obtained on a gram scale in good overall yield in five steps, three of which did not require isolation of the intermediates, starting from the readily available 1‐amino‐4‐oxo‐cyclohexane‐4‐carboxylic acid. Both enantiomers were used for the preparation of pentapeptide models containing Ala, Aib, and Azn. Conformational studies using both spectroscopic techniques (NMR, CD) and molecular dynamics on model 5‐mer peptides showed that the (R)‐Azn isomer possesses a marked helicogenic effect. 相似文献
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Synthesis and Analysis of the Conformational Preferences of 5‐Aminomethyloxazolidine‐2,4‐dione Scaffolds: First Examples of β2‐ and β2, 2‐Homo‐Freidinger Lactam Analogues 下载免费PDF全文
Arianna Greco Sara Tani Rossella De Marco Luca Gentilucci 《Chemistry (Weinheim an der Bergstrasse, Germany)》2014,20(41):13390-13404
Constrained peptidomimetic scaffolds are of considerable interest for the design of therapeutically useful analogues of bioactive peptides. We present the single‐step cyclization of (S)‐ or (R)‐α‐hydroxy‐β2‐ or α‐substituted‐α‐hydroxy‐β2, 2‐amino acids already incorporated within oligopeptides to 5‐aminomethyl‐oxazolidine‐2,4‐dione (Amo) rings. These scaffolds can be regarded as unprecedented β2‐ or β2, 2‐homo‐Freidinger lactam analogues, and can be equipped with a proteinogenic side chain at each residue. In a biomimetic environment, Amo rings act as inducers of extended, semi‐bent or folded geometries, depending on the relative stereochemistry and the presence of α‐substituents. 相似文献
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Dr. Hamed Shaykhalishahi Dr. Aziz Gauhar Michael M. Wördehoff Dr. Clara S. R. Grüning Antonia N. Klein Dr. Oliver Bannach Dr. Matthias Stoldt Prof. Dr. Dieter Willbold Prof. Dr. Torleif Härd Dr. Wolfgang Hoyer 《Angewandte Chemie (International ed. in English)》2015,54(30):8837-8840
Conversion of the intrinsically disordered protein α‐synuclein (α‐syn) into amyloid aggregates is a key process in Parkinson’s disease. The sequence region 35–59 contains β‐strand segments β1 and β2 of α‐syn amyloid fibril models and most disease‐related mutations. β1 and β2 frequently engage in transient interactions in monomeric α‐syn. The consequences of β1–β2 contacts are evaluated by disulfide engineering, biophysical techniques, and cell viability assays. The double‐cysteine mutant α‐synCC, with a disulfide linking β1 and β2, is aggregation‐incompetent and inhibits aggregation and toxicity of wild‐type α‐syn. We show that α‐syn delays the aggregation of amyloid‐β peptide and islet amyloid polypeptide involved in Alzheimer’s disease and type 2 diabetes, an effect enhanced in the α‐synCC mutant. Tertiary interactions in the β1–β2 region of α‐syn interfere with the nucleation of amyloid formation, suggesting promotion of such interactions as a potential therapeutic approach. 相似文献
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Understanding the structure of amyloid‐β (Aβ) aggregates is a key step towards elucidating the pathology of Alzheimer’s disease. In this work, three fragments of the Aβ1–42 protein, Aβ1–25 (DAEFRHDSGYEVHHQKLVFFAEDVG), Aβ25–35 (GSNKGAIIGLM), and Aβ33–42 (GLMVGGVVIA), were synthesized, and their aggregated structures were examined by linear infrared spectroscopy in the amide‐I (mainly the C?O stretching) region. The structures of the formed aggregates were found to be both sequence and pH dependent. The results suggest that instead of forming matured fibrils, as in the case of full‐length Aβ1–42, both Aβ1–25 and Aβ33–42 form a mixture of threadlike β‐sheet fibril, soluble β‐sheet oligomer, and random coil structures. The β‐sheet conformations were found to be mainly antiparallel for the former and both parallel and antiparallel for the latter. However, the Aβ25–35 fragment was found to form assembled fibrils containing predominantly parallel β‐sheets. The conformation and morphology of the aggregates were also confirmed by circular dichroism measurements and transmission electron microscopy. Factors influencing the structures of the aggregates formed by the Aβ fragments were discussed. 相似文献
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pH‐Controlled Formation of a Stable β‐Sheet and Amyloid‐like Fibers from an Amphiphilic Peptide: The Importance of a Tailor‐Made Binding Motif for Secondary Structure Formation 下载免费PDF全文
Dr. Poulami Jana Martin Ehlers Elio Zellermann Dr. Krishnananda Samanta Prof. Dr. Carsten Schmuck 《Angewandte Chemie (International ed. in English)》2016,55(49):15287-15291
The new amphiphilic peptide 1 is composed of alternating cyclohexyl side chains and guanidiniocarbonyl pyrrole (GCP) groups. In contrast to analogue 2 , which contains lysine instead of the GCP groups and only exists as a random coil owing to charge repulsion, peptide 1 forms a stable β‐sheet at neutral pH in aqueous medium. The weakly basic GCP groups (pKa≈7) are key for secondary structure formation as they stabilize the β‐sheet through mutual interactions (formation of a “GCP zipper”). The β‐sheets further aggregate into left‐handed helically twisted fibers. However, β‐sheet formation is completely reversible as a function of pH. At low pH (ca. 4), peptide 1 is unstructured (random coil) as all GCP units are protonated. Only round colloidal particles are observed. The amyloid nature of the fibers formed at neutral pH was confirmed by staining experiments with Congo Red and thioflavin T. Furthermore, at millimolar concentrations, peptide 1 forms a stable hydrogel. 相似文献
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Dr. Julie L. H. Madsen Dr. Claudia U. Hjørringgaard Dr. Brian S. Vad Prof. Dr. Daniel Otzen Prof. Dr. Troels Skrydstrup 《Chemistry (Weinheim an der Bergstrasse, Germany)》2016,22(24):8358-8367
Incorporation of silicon‐containing amino acids in peptides is known to endow the peptide with desirable properties such as improved proteolytic stability and increased lipophilicity. In the presented study, we demonstrate that incorporation of β‐silicon‐β3‐amino acids into the antimicrobial peptide alamethicin provides the peptide with improved membrane permeabilizing properties. A robust synthetic procedure for the construction of β‐silicon‐β3‐amino acids was developed and the amino acid analogues were incorporated into alamethicin at different positions of the hydrophobic face of the amphipathic helix by using SPPS. The incorporation was shown to provide up to 20‐fold increase in calcein release as compared with wild‐type alamethicin. 相似文献