共查询到20条相似文献,搜索用时 15 毫秒
1.
Thioamides are sterically almost identical to their oxoamide counterparts, but they are weaker hydrogen bond acceptors. Therefore, thioamide amino acids are excellent candidates for perturbing the energetics of backbone-backbone H-bonds in proteins and hence should be useful in elucidating protein folding mechanisms in a site-specific manner. Herein, we validate this approach by applying it to probe the dynamic role of interstrand H-bond formation in the folding kinetics of a well-studied β-hairpin, tryptophan zipper. Our results show that reducing the strength of the peptide's backbone-backbone H-bonds, except the one directly next to the β-turn, does not change the folding rate, suggesting that most native interstrand H-bonds in β-hairpins are formed only after the folding transition state. 相似文献
2.
Disulfide bonds between Cys residues in adjacent strands of parallel β-sheets are rare among proteins, which suggests that parallel β-sheet structure is not stabilized by such disulfide cross-links. We report experimental results that show, surprisingly, that an interstrand disulfide bond can stabilize parallel β-sheets formed by an autonomously folding peptide in aqueous solution. NMR analysis reveals that parallel β-sheet structure is terminated beyond the disulfide bond, which causes deviation from the extended backbone conformation at one of the Cys residues. 相似文献
3.
Liu C Sawaya MR Cheng PN Zheng J Nowick JS Eisenberg D 《Journal of the American Chemical Society》2011,133(17):6736-6744
Protein amyloid oligomers have been strongly linked to amyloid diseases and can be intermediates to amyloid fibers. β-Sheets have been identified in amyloid oligomers. However, because of their transient and highly polymorphic properties, the details of their self-association remain elusive. Here we explore oligomer structure using a model system: macrocyclic peptides. Key amyloidogenic sequences from Aβ and tau were incorporated into macrocycles, thereby restraining them to β-strands, but limiting the growth of the oligomers so they may crystallize and cannot fibrillate. We determined the atomic structures for four such oligomers, and all four reveal tetrameric interfaces in which β-sheet dimers pair together by highly complementary, dry interfaces, analogous to steric zippers found in fibers, suggesting a common structure for amyloid oligomers and fibers. In amyloid fibers, the axes of the paired sheets are either parallel or antiparallel, whereas the oligomeric interfaces display a variety of sheet-to-sheet pairing angles, offering a structural explanation for the heterogeneity of amyloid oligomers. 相似文献
4.
This paper reports the use of natural amino acids, the tripeptide β-strand mimic Hao, and the β-turn mimic δ-linked ornithine to generate water-soluble 54-, 78-, and 102-membered-ring macrolactams. These giant macrocycles were efficiently prepared by synthesis of the corresponding protected linear peptides, followed by solution-phase cyclization and deprotection. The protected linear peptide precursors were synthesized on 2-chlorotrityl chloride resin by conventional Fmoc-based solid-phase peptide synthesis. Macrocyclization was typically performed using HCTU and N,N-diisopropylethylamine in DMF at ca. 0.5 mM concentration. The macrocycles were isolated in 13-45% overall yield after HPLC purification and lyophilization. 1D, 2D TOCSY, and 2D ROESY (1)H NMR studies of the 54- and 78-membered-ring macrolactams establish that these compounds fold to form β-sheet structures in aqueous solutions. 相似文献
5.
《Tetrahedron letters》2014,55(50):6873-6877
α-Arylation of β-diketones has been carried out over CuO/aluminosilicate catalyst under ligand-free condition. The reaction conditions were optimized with different solvents, bases, catalyst amounts, and temperatures using acetylacetone and 4-bromobenzaldehyde as a model system. The scope of the catalytic system was extended to include various substituted aryl halides. 27 examples were successfully demonstrated and the yields were ranging from 55% to 94%. C–Br bond was regioselectively activated in the presence of C–Cl bond. Similarly acetylacetone was chemoselectively arylated by 4-bromobenzaldehyde in the presence of dibenzoylacetone. Heterogeneous nature of the catalyst was confirmed by hot-filtration test. The catalyst was also found to be reusable. 相似文献
6.
Understanding the self-assembly behavior of β-sheet peptides is important, not only in constructing bioactive peptide nanostructures, but also in inhibiting uncontrollable protein aggregation in protein-misfolding diseases. Here, the first systematic investigation of combination self-assembly between β-sheet block copolypeptides and CNTs is presented, demonstrating the presence of several different association modes during the combination self-assembly process. Bioactive β-sheet block copolypeptides can self-assemble by themselves, or can be used to functionalize CNT hybrids depending on the situation. This behavior may be important both for fabricating bioactive peptide/CNT hybrids and for controlling/inhibiting protein-misfolding diseases. 相似文献
7.
Robert R. Milburn Ken McRae Johann Chan Jason Tedrow Robert Larsen Margaret Faul 《Tetrahedron letters》2009,50(8):870-9099
The condensation of alkyl phosphonates with aryl esters to give β-ketophosphonates may be carried out at elevated temperatures mediated by LiHMDS under Barbier type conditions. The reaction is scalable, does not require specialized cryogenic equipment, and is general for all aryl and heteroaryl esters examined. 相似文献
8.
<正>A highly effective,new chiral 1,2,3,4-tetrahydroisoquinoline catalyst 1 for the diethylzinc addition to aryl aldehydes has been investigated.Using 10 mol%of this chiral catalyst,secondary alcohols can be obtained in up to 87%yield and 99.5%ee under mild conditions. 相似文献
9.
Inhibition of Cu-amyloid-β by using bifunctional peptides with β-sheet breaker and chelator moieties
Jensen M Canning A Chiha S Bouquerel P Pedersen JT Østergaard J Cuvillier O Sasaki I Hureau C Faller P 《Chemistry (Weinheim an der Bergstrasse, Germany)》2012,18(16):4836-4839
Breaking the mold: Inhibition of toxic amyloid-β (Aβ) aggregates and disruption of Cu-Aβ with subsequent redox-silencing of Cu have been considered promising strategies against Alzheimer's disease. The design and proof of concept of simple peptides containing a Cu-chelating/redox-silencing unit and an Aβ-aggregation inhibition unit (β-sheet breaker) is described (see scheme). 相似文献
10.
An ethoxy-bridged dinuclear indium catalyst was used for the ring opening polymerization of the cyclic ester β-butyrolactone to form the biodegradable polyester poly(hydroxybutyrate) (PHB). The catalyst shows remarkable activity and control during polymerization, allowing for formation of diblock polymers. Addition of high ratios of alcohols to the catalyst leads to fast chain transfer and immortal polymerization. 相似文献
11.
Enol carbamates (O-vinylcarbamates) derived from aromatic or α,β-unsaturated compounds and bearing an N-aryl substituent undergo carbolithiation by nucleophilic attack at the (nominally nucleophilic) β position of the enol double bond. The resulting carbamate-stabilized allylic, propargylic, or benzylic organolithium rearranges with N→C migration of the N-aryl substituent, creating a quaternary carbon α to O. The products may be readily hydrolyzed to yield multiply branched tertiary alcohols in a one-pot tandem reaction, effectively a polarity-reversed nucleophilic β-alkylation-electrophilic α-arylation of an enol equivalent. 相似文献
12.
Kurniawan NA Enemark S Rajagopalan R 《Journal of the American Chemical Society》2012,134(24):10200-10208
Crowded environments inside cells exert significant effects on protein structure, stability, and function, but their effects on (pre)folding dynamics and kinetics, especially at molecular levels, remain ill-understood. Here, we examine the latter for, as an initial candidate, a small de novo β-hairpin using extensive all-atom molecular dynamics simulations for crowder volume fractions φ up to 40%. We find that crowding does not introduce new folding intermediates or misfolded structures, although, as expected, it promotes compact structures and reduces the accessible conformational space. Furthermore, while hydrophobic-collapse-mediated folding is slightly enhanced, the turn-directed zipper mechanism (dominant in crowder-free situations) increases many-fold, becoming even more dominant. Interestingly, φ influences the stability of the folding intermediates (FI(1) and FI(2)) in an apparently counterintuitive manner, which can be understood only by considering specific intrachain interactions and intermediate (and hierarchical) structural transitions. For φ values <20%, native-turn formation is enhanced, and FI(1), characterized by a hairpin structure but slightly mismatched hydrophobic contacts, increases in frequency, thus enhancing eventual folding. However, higher φ values impede native-turn formation, and FI(2), which lacks native turns, re-emerges and increasingly acts as a kinetic trap. The change in the stability of these intermediates with φ strongly correlates with the hierarchical folding stages and their kinetics. The results show that crowding assists intermediate structural changes more by impeding backward transitions than by promoting forward transitions and that a delicate competition between reduction in configuration space and introduction of kinetic traps along the folding route is key to understanding folding kinetics under crowded conditions. 相似文献
13.
The relationships between amino acid sequence, nano-assemblies, and cytotoxicity to neuron cytotoxicity were investigated using β-sheet-forming peptides from Araneus ventricosus spider silk, and amyloid forming peptides Aβ(12-28) (β1), Aβ(28-42) (β2), and full-length Aβ(1-42). Although silk derived peptides formed nano-assemblies, nanofilaments, and nanofibrils with β-sheet contents raging from 24 to 40%, they showed no significant cytotoxicity to neurons. In contrast, nano-assemblies and nanofibrils formed from Aβ peptides with high β-sheet content demonstrated cytotoxicity to the neurons. These differences in cell response between the silk β-sheets and Aβ peptides indicate that the general propensity to form beta sheets and form nanostructures is not sufficient to predict cytotoxicity, while surface charges of the assemblies are significant factors that impact cytotoxicity. 相似文献
14.
Xue-Yi Sun Yulong Zhong Yao-Hua Li Daniel P.Miller Sagar Buttan Xiang-Xiang Wu Yukun Zhang Quan Tang Hong-Wei Tan Jin Zhu Rui Liu Eva Zurek Zhong-Lin Lu Bing Gong 《中国化学快报》2022,33(1):257-261
Five hybrid tetrapeptides, each consisting a central dipeptide segment of α-amino acid residues flanked by two aromatic γ-amino acid residues, are found to fold into well-defined β-hairpin conformations as shown by NMR, computational study, and X-ray structures. The turn loop of this β-hairpin motif accommodates different two-residue α-amino acid sequences from the highly flexible Gly-Gly, to the more restricted D-Pro-Gly. The presence of α-amino acid side chains enhances the stabilities of the ... 相似文献
15.
16.
In this paper, B3LYP and MP2 methods are used to investigate the binding energy of seventeen antiparallel and parallel β-sheet
models. The results indicate that the binding energy obtained from B3LYP calculations is weaker than that obtained from MP2
calculations but the relative binding energy yielded by B3LYP is almost the same as that by MP2. For the antiparallel β-sheets
in which two N-H⋯O=C hydrogen bonds can form either a large hydrogen-bonded ring or a small hydrogen-bonded ring, the binding
energy increases obviously when one large ring unit is added, whereas it only changes slightly when one small ring unit is
added because of the secondary electrostatic repulsive interaction existing in the small ring unit which is estimated to be
about 20 kJ/mol. For the parallel β-sheet models, the binding energy increases almost exactly linearly with the increase of
the chain length. 相似文献
17.
Sinthuvanich C Veiga AS Gupta K Gaspar D Blumenthal R Schneider JP 《Journal of the American Chemical Society》2012,134(14):6210-6217
Several cationic antimicrobial peptides (AMPs) have recently been shown to display anticancer activity via a mechanism that usually entails the disruption of cancer cell membranes. In this work, we designed an 18-residue anticancer peptide, SVS-1, whose mechanism of action is designed to take advantage of the aberrant lipid composition presented on the outer leaflet of cancer cell membranes, which makes the surface of these cells electronegative relative to the surface of noncancerous cells. SVS-1 is designed to remain unfolded and inactive in aqueous solution but to preferentially fold at the surface of cancer cells, adopting an amphiphilic β-hairpin structure capable of membrane disruption. Membrane-induced folding is driven by electrostatic interaction between the peptide and the negatively charged membrane surface of cancer cells. SVS-1 is active against a variety of cancer cell lines such as A549 (lung carcinoma), KB (epidermal carcinoma), MCF-7 (breast carcinoma), and MDA-MB-436 (breast carcinoma). However, the cytotoxicity toward noncancerous cells having typical membrane compositions, such as HUVEC and erythrocytes, is low. CD spectroscopy, appropriately designed peptide controls, cell-based studies, liposome leakage assays, and electron microscopy support the intended mechanism of action, which leads to preferential killing of cancerous cells. 相似文献
18.
Swanekamp RJ DiMaio JT Bowerman CJ Nilsson BL 《Journal of the American Chemical Society》2012,134(12):5556-5559
Amphipathic peptides composed of alternating hydrophobic and hydrophilic amino acids self-assemble into amyloid-inspired, β-sheet nanoribbon fibrils. Herein, we report a new fibril type that is formed from equimolar mixtures of enantiomeric amphipathic peptides (L- and D-(FKFE)(2)). Spectroscopic analysis indicates that these peptides do not self-sort and assemble into enantiomeric fibrils composed of all-l and all-d peptides, but rather coassemble into fibrils that contain alternating L- and D-peptides in a "rippled β-sheet" orientation. Isothermal titration calorimetry indicates an enthalpic advantage for rippled β-sheet coassembly compared to self-sorted β-sheet assembly of enantiomeric peptides. 相似文献
19.
The three-dimensional structures of proteins provide their functions and incorrect folding of its β-strands can be the cause of many diseases. There are two major approaches for determining protein structures: computational prediction and experimental methods that employ technologies such as Cryo-electron microscopy. Due to experimental methods’s high costs, extended wait times for its lengthy processes, and incompleteness of results, computational prediction is an attractive alternative. As the focus of the present paper, β-sheet structure prediction is a major portion of overall protein structure prediction. Prediction of other substructures, such as α-helices, is simpler with lower computational time complexities. Brute force methods are the most common approach and dynamic programming is also utilized to generate all possible conformations. The current study introduces the Subset Sum Approach (SSA) for the direct search space generation method, which is shown to outperform the dynamic programming approach in terms of both time and space. For the first time, the present work has calculated both the state space cardinality of the dynamic programming approach and the search space cardinality of the general brute force approaches. In regard to a set of pruning rules, SSA has demonstrated higher efficiency with respect to both time and accuracy in comparison to state-of-the-art methods. 相似文献
20.
Side-Chain Chemistry Governs Hierarchical Order of Charge-Complementary β-sheet Peptide Coassemblies
Dr. Renjie Liu Xin Dong Dr. Dillon T. Seroski Dr. Bethsymarie Soto Morales Dr. Kong M. Wong Alicia S. Robang Lucas Melgar Prof. Thomas E. Angelini Prof. Anant K. Paravastu Prof. Carol K. Hall Prof. Gregory A. Hudalla 《Angewandte Chemie (International ed. in English)》2023,62(51):e202314531
Self-assembly of proteinaceous biomolecules into functional materials with ordered structures that span length scales is common in nature yet remains a challenge with designer peptides under ambient conditions. This report demonstrates how charged side-chain chemistry affects the hierarchical co-assembly of a family of charge-complementary β-sheet-forming peptide pairs known as CATCH(X+/Y−) at physiologic pH and ionic strength in water. In a concentration-dependent manner, the CATCH(6K+) (Ac-KQKFKFKFKQK-Am) and CATCH(6D−) (Ac-DQDFDFDFDQD-Am) pair formed either β-sheet-rich microspheres or β-sheet-rich gels with a micron-scale plate-like morphology, which were not observed with other CATCH(X+/Y−) pairs. This hierarchical order was disrupted by replacing D with E, which increased fibril twisting. Replacing K with R, or mutating the N- and C-terminal amino acids in CATCH(6K+) and CATCH(6D−) to Qs, increased observed co-assembly kinetics, which also disrupted hierarchical order. Due to the ambient assembly conditions, active CATCH(6K+)-green fluorescent protein fusions could be incorporated into the β-sheet plates and microspheres formed by the CATCH(6K+/6D−) pair, demonstrating the potential to endow functionality. 相似文献