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1.
Current and emerging commercial optical biosensors. 总被引:5,自引:0,他引:5
The field of commercial optical biosensors is rapidly evolving, with new systems and detection methods being developed each year. This review outlines the currently available biosensor hardware and highlights unique features of each platform. Affinity-based biosensor technology, with its high sensitivity, wide versatility and high throughput, is playing a significant role in basic research, pharmaceutical development, and the food and environmental sciences. Likewise, the increasing popularity of biosensors is prompting manufacturers to develop new instrumentation for dedicated applications. We provide a preview of some of the emerging commercial systems that are dedicated to drug discovery, proteomics, clinical diagnostics and routine biomolecular interaction analysis. 相似文献
2.
《Bioorganic & medicinal chemistry》2020,28(9):115437
NDM-1 can hydrolyze nearly all available β-lactam antibiotics, including carbapenems. NDM-1 producing bacterial strains are worldwide threats. It is still very challenging to find a potent NDM-1 inhibitor for clinical use. In our study, we used a metal-binding pharmacophore (MBP) enriched virtual fragment library to screen NDM-1 hits. SPR screening helped to verify the MBP virtual hits and identified a new NDM-1 binder and weak inhibitor A1. A solution NMR study of 15N-labeled NDM-1 showed that A1 disturbed all three residues coordinating the second zinc ion (Zn2) in the active pocket of NDM-1. The perturbation only happened in the presence of zinc ion, indicating that A1 bound to Zn2. Based on the scaffold of A1, we designed and synthesized a series of NDM-1 inhibitors. Several compounds showed synergistic antibacterial activity with meropenem against NDM-1 producing K. pneumoniae. 相似文献
3.
Feng Liu Yalu Cui Fang Yang Zhijue Xu Lin-Tai Da Yan Zhang 《Bioorganic & medicinal chemistry》2019,27(15):3372-3382
Ellagitannin-derived ellagic acid (EA) and colonic metabolite urolithins are functional dietary ingredients for cancer prevention, but the underlying mechanism need elucidation. Mucin-type O-glycosylation, initiated by polypeptide N-acetyl-α-galactosaminyltransferases (ppGalNAc-Ts), fine-tunes multiple biological processes and is closely associated with cancer progression. Herein, we aim to explore how specific tannin-based polyphenols affect tumor behavior of colorectal cancer cells (CRC) by modulating O-glycosylation. Utilizing HPLC-based enzyme assay, we find urolithin D (UroD), EA and gallic acid (GA) potently inhibit ppGalNAc-Ts. In particular, UroD inhibits ppGalNAc-T2 through a peptide/protein-competitive manner with nanomolar affinity. Computational simulations combined with site-directed mutagenesis further support the inhibitors’ mode of action. Moreover, lectin analysis and metabolic labelling reveal that UroD can reduce cell O-glycans but not N-glycans. Transwell experiments prove that UroD inhibits migration and invasion of CRC cells. Our work proves that specific tannin-based polyphenols can potently inhibit ppGalNAc-Ts activity to reduce cell O-glycosylation and lead to lowering the migration and invasion of CRC cells, suggesting that disturbance of mucin-type O-glycosylation is an important mechanism for the function of dietary polyphenols. 相似文献
4.
Nikolaos G. Sgourakis Nathan A. May Lisa F. Boyd Jinfa Ying Ad Bax David H. Margulies 《The Journal of biological chemistry》2015,290(48):28857-28868
As part of its strategy to evade detection by the host immune system, murine cytomegalovirus (MCMV) encodes three proteins that modulate cell surface expression of major histocompatibility complex class I (MHC-I) molecules: the MHC-I homolog m152/gp40 as well as the m02-m16 family members m04/gp34 and m06/gp48. Previous studies of the m04 protein revealed a divergent Ig-like fold that is unique to immunoevasins of the m02-m16 family. Here, we engineer and characterize recombinant m06 and investigate its interactions with full-length and truncated forms of the MHC-I molecule H2-Ld by several techniques. Furthermore, we employ solution NMR to map the interaction footprint of the m06 protein on MHC-I, taking advantage of a truncated H2-Ld, “mini-H2-Ld,” consisting of only the α1α2 platform domain. Mini-H2-Ld refolded in vitro with a high affinity peptide yields a molecule that shows outstanding NMR spectral features, permitting complete backbone assignments. These NMR-based studies reveal that m06 binds tightly to a discrete site located under the peptide-binding platform that partially overlaps with the β2-microglobulin interface on the MHC-I heavy chain, consistent with in vitro binding experiments showing significantly reduced complex formation between m06 and β2-microglobulin-associated MHC-I. Moreover, we carry out NMR relaxation experiments to characterize the picosecond-nanosecond dynamics of the free mini-H2-Ld MHC-I molecule, revealing that the site of interaction is highly ordered. This study provides insight into the mechanism of the interaction of m06 with MHC-I, suggesting a structural manipulation of the target MHC-I molecule at an early stage of the peptide-loading pathway. 相似文献
5.
Thai Leong Yap Zhiping Jiang Frank Heinrich James M. Gruschus Candace M. Pfefferkorn Marilia Barros Joseph E. Curtis Ellen Sidransky Jennifer C. Lee 《The Journal of biological chemistry》2015,290(2):744-754
Mutations in glucocerebrosidase (GCase), the enzyme deficient in Gaucher disease, are a common genetic risk factor for the development of Parkinson disease and related disorders, implicating the role of this lysosomal hydrolase in the disease etiology. A specific physical interaction exists between the Parkinson disease-related protein α-synuclein (α-syn) and GCase both in solution and on the lipid membrane, resulting in efficient enzyme inhibition. Here, neutron reflectometry was employed as a first direct structural characterization of GCase and α-syn·GCase complex on a sparsely-tethered lipid bilayer, revealing the orientation of the membrane-bound GCase. GCase binds to and partially inserts into the bilayer with its active site most likely lying just above the membrane-water interface. The interaction was further characterized by intrinsic Trp fluorescence, circular dichroism, and surface plasmon resonance spectroscopy. Both Trp fluorescence and neutron reflectometry results suggest a rearrangement of loops surrounding the catalytic site, where they extend into the hydrocarbon chain region of the outer leaflet. Taking advantage of contrasting neutron scattering length densities, the use of deuterated α-syn versus protiated GCase showed a large change in the membrane-bound structure of α-syn in the complex. We propose a model of α-syn·GCase on the membrane, providing structural insights into inhibition of GCase by α-syn. The interaction displaces GCase away from the membrane, possibly impeding substrate access and perturbing the active site. GCase greatly alters membrane-bound α-syn, moving helical residues away from the bilayer, which could impact the degradation of α-syn in the lysosome where these two proteins interact. 相似文献
6.
Xi Chen Kathrin Hnida Melissa Ann Graewert Jan Terje Andersen Rasmus Iversen Anne Tuukkanen Dmitri Svergun Ludvig M. Sollid 《The Journal of biological chemistry》2015,290(35):21365-21375
Antibodies to the autoantigen transglutaminase 2 (TG2) are a hallmark of celiac disease. We have studied the interaction between TG2 and an anti-TG2 antibody (679-14-E06) derived from a single gut IgA plasma cell of a celiac disease patient. The antibody recognizes one of four identified epitopes targeted by antibodies of plasma cells of the disease lesion. The binding interface was identified by small angle x-ray scattering, ab initio and rigid body modeling using the known crystal structure of TG2 and the crystal structure of the antibody Fab fragment, which was solved at 2.4 Å resolution. The result was confirmed by testing binding of the antibody to TG2 mutants by ELISA and surface plasmon resonance. TG2 residues Arg-116 and His-134 were identified to be critical for binding of 679-14-E06 as well as other epitope 1 antibodies. In contrast, antibodies directed toward the two other main epitopes (epitopes 2 and 3) were not affected by these mutations. Molecular dynamics simulations suggest interactions of 679-14-E06 with the N-terminal domain of TG2 via the CDR2 and CDR3 loops of the heavy chain and the CDR2 loop of the light chain. In addition there were contacts of the framework 3 region of the heavy chain with the catalytic domain of TG2. The results provide an explanation for the biased usage of certain heavy and light chain gene segments by epitope 1-specific antibodies in celiac disease. 相似文献
7.
Marjolein Glas H. Bart van den Berg van Saparoea Stephen H. McLaughlin Winfried Roseboom Fan Liu Gregory M. Koningstein Alexander Fish Tanneke den Blaauwen Albert J. R. Heck Luitzen de Jong Wilbert Bitter Iwan J. P. de Esch Joen Luirink 《The Journal of biological chemistry》2015,290(35):21498-21509
Cell division in Escherichia coli involves a set of essential proteins that assembles at midcell to form the so-called divisome. The divisome regulates the invagination of the inner membrane, cell wall synthesis, and inward growth of the outer membrane. One of the divisome proteins, FtsQ, plays a central but enigmatic role in cell division. This protein associates with FtsB and FtsL, which, like FtsQ, are bitopic inner membrane proteins with a large periplasmic domain (denoted FtsQp, FtsBp, and FtsLp) that is indispensable for the function of each protein. Considering the vital nature and accessible location of the FtsQBL complex, it is an attractive target for protein-protein interaction inhibitors intended to block bacterial cell division. In this study, we expressed FtsQp, FtsBp, and FtsLp individually and in combination. Upon co-expression, FtsQp was co-purified with FtsBp and FtsLp from E. coli extracts as a stable trimeric complex. FtsBp was also shown to interact with FtsQp in the absence of FtsLp albeit with lower affinity. Interactions were mapped at the C terminus of the respective domains by site-specific cross-linking. The binding affinity and 1:1:1 stoichiometry of the FtsQpBpLp complex and the FtsQpBp subcomplex were determined in complementary surface plasmon resonance, analytical ultracentrifugation, and native mass spectrometry experiments. 相似文献
8.
Yao Wu Peng Chen Li Sun Shengtao Yuan Zujue Cheng Ligong Lu Hongzhi Du Meixiao Zhan 《Journal of cellular and molecular medicine》2020,24(17):9495-9506
Sepiapterin reductase, a homodimer composed of two subunits, plays an important role in the biosynthesis of tetrahydrobiopterin. Furthermore, sepiapterin reductase exhibits a wide distribution in different tissues and is associated with many diseases, including brain dysfunction, chronic pain, cardiovascular disease and cancer. With regard to drugs targeting sepiapterin reductase, many compounds have been identified and provide potential methods to treat various diseases. However, the underlying mechanism of sepiapterin reductase in many biological processes is unclear. Therefore, this article summarized the structure, distribution and function of sepiapterin reductase, as well as the relationship between sepiapterin reductase and different diseases, with the aim of finding evidence to guide further studies on the molecular mechanisms and the potential clinical value of sepiapterin reductase. In particular, the different effects induced by the depletion of sepiapterin reductase or the inhibition of the enzyme suggest that the non‐enzymatic activity of sepiapterin reductase could function in certain biological processes, which also provides a possible direction for sepiapterin reductase research. 相似文献
9.
Surface Plasmon Resonance (SPR) biosensor technology has been successfully used for the detection of various analytes such as proteins, drugs, DNA, and microorganisms. SPR-based immunosensors that coupled with a specific antigen-antibody reaction, have become a promising tool for the quantification of bacteria as it offers sensitive, specific, rapid, and label-free detection. In this paper, we review the important issues in the development of SPR-based immunoassays for bacteria detection, concentrating on instrumentation, surface functionalization, liquid handling, and surface regeneration. In addition, this review touches on the recent advances in SPR biosensing for sensitivity enhancement. 相似文献
10.
Young-Seok Shon Hyung Y. Choi Michael S. Guerrero Chuhee Kwon 《Plasmonics (Norwell, Mass.)》2009,4(2):95-105
This article presents a concise review of preparation methods for transparent nanostructured films, with an emphasis on their
current applications in transmission-localized surface plasmon resonance (T-LSPR) sensing. One of the first methods used for
the fabrication of transparent nanostructured metal films is a direct vacuum evaporation of thin gold films. Self-induced
formations of small gold islands result in transparent nanostructured gold arrays. The most well-established method is a nanosphere
lithography developed by Van Duyne. Nanotriangular island arrays with controlled size and optical properties can be fabricated
by this protocol. A different nanolithography method known as focused ion beam milling is reported and used for the fabrication
of nanohole arrays. Simple assembly of solution-phase synthesized nanoparticles has also been utilized for the preparation
of nanoparticle arrays capable of T-LSPR sensing. Lastly, this article also describes a new preparation strategy, in which
self-assembly/thermolysis of nanoparticle multilayers is employed to obtain transparent nanoisland architectures on glass
substrates. 相似文献