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131.
Yohei Saito Atsushi Mizokami Kouji Izumi Renato Naito Masuo Goto Kyoko Nakagawa-Goto 《Molecules (Basel, Switzerland)》2021,26(9)
α-Trifluoromethyl chalcones were prepared and evaluated for their antiproliferative activities against androgen-independent prostate cancer cell lines as well as five additional types of human tumor cell lines. The most potent chalcone 5 showed superior antitumor activity in vivo with both oral and intraperitoneal administration at 3 mg/kg. Cell-based mechanism of action studies demonstrated that 5 induced cell accumulation at sub-G1 and G2/M phases without interfering with microtubule polymerization. Furthermore, several cancer cell growth-related proteins were identified by using chalcone 5 as a bait for the affinity purification of binding proteins. 相似文献
132.
α-Actinin involvement in Z-disk assembly during skeletal muscle C2C12 cells in vitro differentiation
α-Actinin is involved in the assembly and maintenance of muscle fibers. α-Actinin is required to cross-link actin filaments and to connect the actin cytoskeleton to the cell membrane and it is necessary for the attachment of actin filaments to Z-disks in skeletal muscle fibers and to dense bodies in smooth muscle ones. In addition to its mechanical role, sarcomeric α-actinin interacts with proteins involved in a variety of signaling and metabolic pathways.The aim of this work is to monitor Z-disk formation, in order to clear up the role of sarcomeric α-actinin in undifferentiated stage, after 4 days of differentiation (intermediate differentiation stage) and after 7 days of differentiation (fully differentiated stage). For this purpose, C2C12 murine skeletal muscle cells, grown in vitro, were analyzed at three time points of differentiation.Confocal laser scanner microscopy and transmission electron microscopy have been utilized for α-actinin immunolocalization.Both techniques reveal that in undifferentiated cells labeling appears uniformly distributed in the cytoplasm with punctate α-actinin Z-bodies. Moreover, we found that when differentiation is induced, α-actinin links at first membrane-associated proteins, then it aligns longitudinally across the cytoplasm and finally binds actin, giving rise to Z-disks. These findings evidence α-actinin involvement in sarcomeric development, suggesting for this protein an important role in stabilizing the muscle contractile apparatus. 相似文献
133.
Overview of software options for processing,analysis and interpretation of mass spectrometric proteomic data 下载免费PDF全文
Recently, the interests in proteomics have been intensively increased, and the proteomic methods have been widely applied to many problems in cell biology. If the age of 1990s is considered to be a decade of genomics, we can claim that the following years of the new century is a decade of proteomics. The rapid evolution of proteomics has continued through these years, with a series of innovations in separation techniques and the core technologies of two‐dimensional gel electrophoresis and MS. Both technologies are fueled by automation and high throughput computation for profiling of proteins from biological systems. As Patterson ever mentioned, ‘data analysis is the Achilles heel of proteomics and our ability to generate data now outstrips our ability to analyze it’. The development of automatic and high throughput technologies for rapid identification of proteins is essential for large‐scale proteome projects and automatic protein identification and characterization is essential for high throughput proteomics. This review provides a snap shot of the tools and applications that are available for mass spectrometric high throughput biocomputation. The review starts with a brief introduction of proteomics and MS. Computational tools that can be employed at various stages of analysis are presented, including that for data processing, identification, quantification, and the understanding of the biological functions of individual proteins and their dynamic interactions. The challenges of computation software development and its future trends in MS‐based proteomics have also been speculated. Copyright © 2014 John Wiley & Sons, Ltd. 相似文献
134.
Andreas Bornø Carl J. Hulston Gerrit van Hall 《Journal of mass spectrometry : JMS》2014,49(8):674-680
In the present study, different MS methods for the determination of human muscle protein fractional synthesis rate (FSR) using [ring‐13C6]phenylalanine as a tracer were evaluated. Because the turnover rate of human skeletal muscle is slow, only minute quantities of the stable isotopically labeled amino acid will be incorporated within the few hours of a typical laboratory experiment. GC combustion isotope ratio MS (GC‐C‐IRMS) has thus far been considered the ‘gold’ standard for the precise measurements of these low enrichment levels. However, advances in liquid chromatography‐tandem MS (LC‐MS/MS) and GC‐tandem MS (GC‐MS/MS) have made these techniques an option for human muscle FSR measurements. Human muscle biopsies were freeze dried, cleaned, and hydrolyzed, and the amino acids derivatized using either N‐acetyl‐n‐propyl, phenylisothiocyanate, or N‐methyl‐N‐(tert‐butyldimethylsilyl)trifluoroacetamide (MTBSTFA) for GC‐C‐IRMS, LC‐MS/MS, and GC‐MS/MS analysis, respectively. A second derivative, heptafluorobutyric acid (HFBA), was also used for GC‐MS/MS analysis as an alternative for MTBSTFA. The machine reproducibility or the coefficients of variation for delta tracer‐tracee‐ratio measurements (delta tracer‐tracee‐ratio values around 0.0002) were 2.6%, 4.1%, and 10.9% for GC‐C‐IRMS, LC‐MS/MS, and GC‐MS/MS (MTBSTFA), respectively. FSR determined with LC‐MS/MS compared well with GC‐C‐IRMS and so did the GC‐MS/MS when using the HFBA derivative (linear fit Y = 1.08 ± 0.10, X + 0.0049 ± 0.0061, r = 0.89 ± 0.01, P < 0.0001). In conclusion, (1) IRMS still offers the most precise measurement of human muscle FSR, (2) LC‐MS/MS comes quite close and is a good alternative when tissue quantities are too small for GC‐C‐IRMS, and (3) If GC‐MS/MS is to be used, then the HFBA derivative should be used instead of MTBSTFA, which gave unacceptably high variability. Copyright © 2014 John Wiley & Sons, Ltd. 相似文献
135.
Spectroscopic and Computational Study of a Nonheme Iron Nitrosyl Center in a Biosynthetic Model of Nitric Oxide Reductase 下载免费PDF全文
Dr. Saumen Chakraborty Julian Reed Matthew Ross Dr. Mark J. Nilges Igor D. Petrik Dr. Soumya Ghosh Prof. Dr. Sharon Hammes‐Schiffer Prof. Dr. J. Timothy Sage Prof. Dr. Yong Zhang Prof. Dr. Charles E. Schulz Prof. Dr. Yi Lu 《Angewandte Chemie (International ed. in English)》2014,53(9):2417-2421
A major barrier to understanding the mechanism of nitric oxide reductases (NORs) is the lack of a selective probe of NO binding to the nonheme FeB center. By replacing the heme in a biosynthetic model of NORs, which structurally and functionally mimics NORs, with isostructural ZnPP, the electronic structure and functional properties of the FeB nitrosyl complex was probed. This approach allowed observation of the first S=3/2 nonheme {FeNO}7 complex in a protein‐based model system of NOR. Detailed spectroscopic and computational studies show that the electronic state of the {FeNO}7 complex is best described as a high spin ferrous iron (S=2) antiferromagnetically coupled to an NO radical (S= 1/2) [Fe2+‐NO.]. The radical nature of the FeB‐bound NO would facilitate N? N bond formation by radical coupling with the heme‐bound NO. This finding, therefore, supports the proposed trans mechanism of NO reduction by NORs. 相似文献
136.
Multi‐Colored Fibers by Self‐Assembly of DNA,Histone Proteins,and Cationic Conjugated Polymers 下载免费PDF全文
Fengyan Wang Zhang Liu Bing Wang Dr. Liheng Feng Prof. Libing Liu Prof. Fengting Lv Prof. Yilin Wang Prof. Shu Wang 《Angewandte Chemie (International ed. in English)》2014,53(2):424-428
The development of biomolecular fiber materials with imaging ability has become more and more useful for biological applications. In this work, cationic conjugated polymers (CCPs) were used to construct inherent fluorescent microfibers with natural biological macromolecules (DNA and histone proteins) through the interfacial polyelectrolyte complexation (IPC) procedure. Isothermal titration microcalorimetry results show that the driving forces for fiber formation are electrostatic and hydrophobic interactions, as well as the release of counterions and bound water molecules. Color‐encoded IPC fibers were also obtained based on the co‐assembly of DNA, histone proteins, and blue‐, green‐, or red‐ (RGB‐) emissive CCPs by tuning the fluorescence resonance energy‐transfer among the CCPs at a single excitation wavelength. The fibers could encapsulate GFP‐coded Escherichia coli BL21, and the expression of GFP proteins was successfully regulated by the external environment of the fibers. These multi‐colored fibers show a great potential in biomedical applications, such as biosensor, delivery, and release of biological molecules and tissue engineering. 相似文献
137.
Mild Bioconjugation Through the Oxidative Coupling of ortho‐Aminophenols and Anilines with Ferricyanide 下载免费PDF全文
Allie C. Obermeyer John B. Jarman Chawita Netirojjanakul Kareem El Muslemany Prof. Dr. Matthew B. Francis 《Angewandte Chemie (International ed. in English)》2014,53(4):1057-1061
Using a small‐molecule‐based screen, ferricyanide was identified as a mild and efficient oxidant for the coupling of anilines and o‐aminophenols on protein substrates. This reaction is compatible with thiols and 1,2‐diols, allowing its use in the creation of complex bioconjugates for use in biotechnology and materials applications. 相似文献
138.
Interaction with the Surrounding Water Plays a Key Role in Determining the Aggregation Propensity of Proteins 下载免费PDF全文
Dr. Song‐Ho Chong Prof. Sihyun Ham 《Angewandte Chemie (International ed. in English)》2014,53(15):3961-3964
Understanding the molecular determinants of the relative propensities of proteins to aggregate in a cellular environment is a central issue for treating protein‐aggregation diseases and developing peptide‐based therapeutics. Despite the expectation that protein aggregation can largely be attributed to direct protein–protein interactions, a crucial role the surrounding water in determining the aggregation propensity of proteins both in vitro and in vivo was identified. The overall protein hydrophobicity, defined solely by the hydration free energy of a protein in its monomeric state sampling its equilibrium structures, was shown to be the predominant determinant of protein aggregation propensity in aqueous solution. Striking discrimination of positively and negatively charged residues by the surrounding water was also found. This effect depends on the protein net charge and plays a crucial role in regulating the solubility of the protein. These results pave the way for the design of aggregation‐resistant proteins as biotherapeutics. 相似文献
139.
Phosphatidylcholine‐Coated Iron Oxide Nanomicelles for In Vivo Prolonged Circulation Time with an Antibiofouling Protein Corona 下载免费PDF全文
Hugo Groult Dr. Jesús Ruiz‐Cabello Ana Victoria Lechuga‐Vieco Dr. Jesús Mateo Dr. Marina Benito Izaskun Bilbao Dr. María Paz Martínez‐Alcázar Dr. Juan. Antonio Lopez Dr. Jesús Vázquez Dr. Fernando F. Herranz 《Chemistry (Weinheim an der Bergstrasse, Germany)》2014,20(50):16662-16671
We report the synthesis of micellar phosphatidylcholine‐coated superparamagnetic iron oxide nanoparticles as a new long circulation contrast agents for magnetic resonance imaging. Oleic acid‐coated Fe3O4 nanoparticles were first prepared through thermal degradation and then encapsulated into small clusters with a phosphatidylcholine coating to obtain hydrophilic nanomicelles. A thorough characterization confirmed the chemical nature of the coating and the excellent colloidal stability of these nanomicelles in aqueous media. Magnetization and relaxivity properties proved their suitability as magnetic resonance imaging (MRI) contrast agent and in vitro cell viability data showed low toxicity. Vascular lifetime and elimination kinetics in the liver were assessed by blood relaxometry and by in vivo MRI in rats and compared with “control” particles prepared with a polyethylene glycol derivative. These micellar particles had a lifetime in blood of more than 10 h, much longer than the control nanoparticles (≈2 h), which is remarkable considering that the coating molecule is a small biocompatible zwitterionic phospholipid. The protein corona was characterized after incubation with rat serum at different times by high‐throughput proteomics, showing a higher proportion of bound apolipoproteins and other dysopsonins for the phosphatidylcholine particles. The antibiofouling properties of this corona and its resistance to the adsorption of proteins corroborate the observed enhanced stability and prolonged systemic circulation. 相似文献
140.
Serine‐Selective Aerobic Cleavage of Peptides and a Protein Using a Water‐Soluble Copper–Organoradical Conjugate 下载免费PDF全文
Yohei Seki Dr. Kana Tanabe Dr. Daisuke Sasaki Dr. Youhei Sohma Dr. Kounosuke Oisaki Prof. Dr. Motomu Kanai 《Angewandte Chemie (International ed. in English)》2014,53(25):6501-6505
The site‐specific cleavage of peptide bonds is an important chemical modification of biologically relevant macromolecules. The reaction is not only used for routine structural determination of peptides, but is also a potential artificial modulator of protein function. Realizing the substrate scope beyond the conventional chemical or enzymatic cleavage of peptide bonds is, however, a formidable challenge. Here we report a serine‐selective peptide‐cleavage protocol that proceeds at room temperature and near neutral pH value, through mild aerobic oxidation promoted by a water‐soluble copper–organoradical conjugate. The method is applicable to the site‐selective cleavage of polypeptides that possess various functional groups. Peptides comprising D ‐amino acids or sensitive disulfide pairs are competent substrates. The system is extendable to the site‐selective cleavage of a native protein, ubiquitin, which comprises more than 70 amino acid residues. 相似文献