排序方式: 共有56条查询结果,搜索用时 15 毫秒
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Cristina Sisu Andrew J. Baron Hilbert M. Branderhorst Dr. Simon D. Connell Dr. Carel A. G. M. Weijers Dr. Renko de Vries Dr. Edward D. Hayes Aliaksei V. Pukin Michel Gilbert Dr. Roland J. Pieters Dr. Han Zuilhof Prof. Dr. Gerben M. Visser Dr. W. Bruce Turnbull Dr. 《Chembiochem : a European journal of chemical biology》2009,10(2):329-337
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Emil Johansson Rmi Caraballo Daniel L. Hurdiss Nitesh Mistry C. David Andersson Rebecca F. Thompson Neil A. Ranson Georg Zocher Thilo Stehle Niklas Arnberg Mikael Elofsson 《International journal of molecular sciences》2021,22(16)
Coxsackievirus A24 variant (CVA24v) is the primary causative agent of the highly contagious eye infection designated acute hemorrhagic conjunctivitis (AHC). It is solely responsible for two pandemics and several recurring outbreaks of the disease over the last decades, thus affecting millions of individuals throughout the world. To date, no antiviral agents or vaccines are available for combating this disease, and treatment is mainly supportive. CVA24v utilizes Neu5Ac-containing glycans as attachment receptors facilitating entry into host cells. We have previously reported that pentavalent Neu5Ac conjugates based on a glucose-scaffold inhibit CVA24v infection of human corneal epithelial cells. In this study, we report on the design and synthesis of scaffold-replaced pentavalent Neu5Ac conjugates and their effect on CVA24v cell transduction and the use of cryogenic electron microscopy (cryo-EM) to study the binding of these multivalent conjugates to CVA24v. The results presented here provide insights into the development of Neu5Ac-based inhibitors of CVA24v and, most significantly, the first application of cryo-EM to study the binding of a multivalent ligand to a lectin. 相似文献
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A Peptide‐Functionalized Polymer as a Minimal Scaffold Protein To Enhance Cluster Formation in Early T Cell Signal Transduction 下载免费PDF全文
J. Joris Witsenburg Michael D. Sinzinger Dr. Oda Stoevesandt Dr. Ivo R. Ruttekolk Dr. Günter Roth Dr. Merel J. W. Adjobo‐Hermans Prof. Dr. Roland Brock 《Chembiochem : a European journal of chemical biology》2015,16(4):602-610
In cellular signal transduction, scaffold proteins provide binding sites to organize signaling proteins into supramolecular complexes and act as nodes in the signaling network. Furthermore, multivalent interactions between the scaffold and other signaling proteins contribute to the formation of protein microclusters. Such microclusters are prominent in early T cell signaling. Here, we explored the minimal structural requirement for a scaffold protein by coupling multiple copies of a proline‐rich peptide corresponding to an interaction motif for the SH3 domain of the adaptor protein GADS to an N‐(2‐hydroxypropyl)methacrylamide polymer backbone. When added to GADS‐containing cell lysates, these scaffolds (but not individual peptides) promoted the binding of GADS to peptide microarrays. This can be explained by the cross‐linking of GADS into larger complexes. Furthermore, following import into Jurkat T cell leukemia cells, this synthetic scaffold enhanced the formation of microclusters of signaling proteins. 相似文献
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In this article we investigate the effect of multivalency in chiral recognition. To this end, we measured the host-guest interaction of a β-cyclodextrin dimer with divalent chiral guests. We report the synthesis of carbohydrate-based water soluble chiral guests functionalized with two borneol, menthol, or isopinocampheol units in either (+) or (-) configuration. We determined the interaction of these divalent guests with a β-cyclodextrin dimer using isothermal titration calorimetry. It was found that-in spite of a highly unfavorable conformation-the cyclodextrin dimer binds to guest dimers with an increased enantioselectivity, which clearly reflects the effect of multivalency. 相似文献
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Shan M Bujotzek A Abendroth F Wellner A Gust R Seitz O Weber M Haag R 《Chembiochem : a European journal of chemical biology》2011,12(17):2587-2598
The estrogen receptor binding affinities of bivalent raloxifene ligands tethered by flexible spacers of different lengths have been evaluated in vitro. Two bivalent binding modes, intra- and intermolecular, were hypothesized to explain their different binding properties. The binding affinities of these bivalent ligands in an aqueous environment are influenced by their conformations, which can be determined by 2D NMR and UV spectral methods. Moreover, computer modeling and simulations were performed to explain the binding modes of these bivalent ligands and to estimate the conformational entropy difference between their unbound and bound states. It was found that bivalent ligands tethered by long spacers had weaker binding affinities because of the shielding of the binding moieties that results from their folded conformations; those tethered by short spacers had stronger affinities because they exposed their ligands to the receptor. 相似文献
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Chafekar SM Malda H Merkx M Meijer EW Viertl D Lashuel HA Baas F Scheper W 《Chembiochem : a European journal of chemical biology》2007,8(15):1857-1864
The key pathogenic event in the onset of Alzheimer's disease (AD) is the aggregation of beta-amyloid (Abeta) peptides into toxic aggregates. Molecules that interfere with this process might act as therapeutic agents for the treatment of AD. The amino acid residues 16-20 (KLVFF) are known to be essential for the aggregation of Abeta. In this study, we have used a first-generation dendrimer as a scaffold for the multivalent display of the KLVFF peptide. The effect of four KLVFF peptides attached to the dendrimer (K(4)) on Abeta aggregation was compared to the effect of monomeric KLVFF (K(1)). Our data show that K(4) very effectively inhibits the aggregation of low-molecular-weight and protofibrillar Abeta(1-42) into fibrils, in a concentration-dependent manner, and much more potently than K(1). Moreover, we show that K(4) can lead to the disassembly of existing aggregates. Our data lead us to propose that conjugates that bear multiple copies of KLVFF might be useful as therapeutic agents for the treatment of Alzheimer's disease. 相似文献
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Shione Kamoshita Saho Matsui Nanako Suto Prof. Kaori Sakurai 《Chembiochem : a European journal of chemical biology》2022,23(4):e202100388
We have designed and synthesized six different multivalent electrophiles as carbohydrate affinity labeling probes. Evaluation of the reactivity of the electrophiles against peanut agglutinin (PNA) and Ricinus communis agglutinin (RCA) showed that p- and m-aryl sulfonyl fluoride are effective protein reactive groups that label carbohydrate binding lectins in a ligand-dependent fashion at a nanomolar probe concentration. Analysis of the selectivity of affinity labeling in the presence of excess BSA as a nonspecific protein indicated that m-arylsulfonyl fluoride is a more selective protein-reactive group, albeit with attenuated reactivity. Further analysis showed that the labeling efficiency of the multivalent electrophilic probes can be improved by employing reaction conditions involving 25 °C instead of typically employed 4 °C. Both isomers of arylsulfonyl fluoride groups together represent promising affinity labels for target identification studies that could serve as more efficient alternatives to photoreactive groups. 相似文献
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