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1.
《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2017,129(50):16175-16179
In this study, an epitope‐imprinting strategy was employed for the dynamic display of bioactive ligands on a material interface. An imprinted surface was initially designed to exhibit specific affinity towards a short peptide (i.e., the epitope). This surface was subsequently used to anchor an epitope‐tagged cell‐adhesive peptide ligand (RGD: Arg‐Gly‐Asp). Owing to reversible epitope‐binding affinity, ligand presentation and thereby cell adhesion could be controlled. As compared to current strategies for the fabrication of dynamic biointerfaces, for example, through reversible covalent or host–guest interactions, such a molecularly tunable dynamic system based on a surface‐imprinting process may unlock new applications in in situ cell biology, diagnostics, and regenerative medicine. 相似文献
2.
Vincenzo Abbate Nunzianda Frascione Sukhvinder S. Bansal 《Journal of polymer science. Part A, Polymer chemistry》2010,48(8):1721-1731
Molecularly imprinted hydrogels for the capture of the peptide hormone hepcidin were prepared by water‐in‐oil (w/o) suspension polymerization under mild conditions. Spherical and relatively uniformly sized gel beads were routinely obtained after optimization of the synthetic methodology. The polymers were analyzed by Fourier transform infrared spectroscopy, optical microscopy, and scanning electron microscopy. Although the imprinted materials exhibited higher affinity towards the epitope template (hepcidin N‐terminus) than their corresponding blank polymers, the full‐length target peptide was found strongly bound to all the hydrogels tested. However, by using whole fluorescent hepcidin as the print species, the imprinting effect was more pronounced. Moreover, bovine serum albumin did not bind to the poly N‐isopropylacrylamide (PNIPAm)‐based polymers. Thus, polymeric “sponges” for biomacromolecules with size‐exclusion effect were developed, useful for peptide concentration, immobilization and/or purification from serum samples. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 1721–1731, 2010 相似文献
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A Cyclized Helix‐Loop‐Helix Peptide as a Molecular Scaffold for the Design of Inhibitors of Intracellular Protein–Protein Interactions by Epitope and Arginine Grafting
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Dr. Daisuke Fujiwara Hidekazu Kitada Masahiro Oguri Toshio Nishihara Dr. Masataka Michigami Dr. Kazunori Shiraishi Dr. Eiji Yuba Dr. Ikuhiko Nakase Haeri Im Sunhee Cho Dr. Jong Young Joung Prof. Seiji Kodama Prof. Kenji Kono Prof. Sihyun Ham Prof. Ikuo Fujii 《Angewandte Chemie (International ed. in English)》2016,55(36):10612-10615
The design of inhibitors of intracellular protein–protein interactions (PPIs) remains a challenge in chemical biology and drug discovery. We propose a cyclized helix‐loop‐helix (cHLH) peptide as a scaffold for generating cell‐permeable PPI inhibitors through bifunctional grafting: epitope grafting to provide binding activity, and arginine grafting to endow cell‐permeability. To inhibit p53–HDM2 interactions, the p53 epitope was grafted onto the C‐terminal helix and six Arg residues were grafted onto another helix. The designed peptide cHLHp53‐R showed high inhibitory activity for this interaction, and computational analysis suggested a binding mode for HDM2. Confocal microscopy of cells treated with fluorescently labeled cHLHp53‐R revealed cell membrane penetration and cytosolic localization. The peptide inhibited the growth of HCT116 and LnCap cancer cells. This strategy of bifunctional grafting onto a well‐structured peptide scaffold could facilitate the generation of inhibitors for intracellular PPIs. 相似文献
5.
《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2017,129(25):7194-7198
Protein corona formation was regulated on the surface in vivo by molecular imprinting to enable polymeric nanogels to acquire stealth upon intravenous administration. Albumin, the most abundant protein in blood, was selected as a distinct protein component of protein corona for preparing molecularly imprinted nanogels (MIP‐NGs) to form an albumin‐rich protein corona. Intravital fluorescence resonance energy transfer imaging of rhodamine‐labeled albumin and fluorescein‐conjugated MIP‐NGs showed that albumin was captured by MIP‐NGs immediately after injection, forming an albumin‐rich protein corona. MIP‐NGs circulated in the blood longer than those of non‐albumin‐imprinted nanogels, with almost no retention in liver tissue. MIP‐NGs also passively accumulated in tumor tissue. These data suggest that this strategy, based on regulation of the protein corona in vivo, may significantly influence the development of drug nanocarriers for cancer therapy. 相似文献
6.
Inhibition of Amyloid Fibril Growth and Dissolution of Amyloid Fibrils by Curcumin–Gold Nanoparticles
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Sharbari Palmal Amit Ranjan Maity Brijesh Kumar Singh Sreetama Basu Prof. Nihar R. Jana Dr. Nikhil R. Jana 《Chemistry (Weinheim an der Bergstrasse, Germany)》2014,20(20):6184-6191
Inhibition of amyloid fibrillation and clearance of amyloid fibrils/plaques are essential for the prevention and treatment of various neurodegenerative disorders involving protein aggregation. Herein, we report curcumin‐functionalized gold nanoparticles (Au‐curcumin) of hydrodynamic diameter 10–25 nm, which serve to inhibit amyloid fibrillation and disintegrate/dissolve amyloid fibrils. In nanoparticle form, curcumin is water‐soluble and can efficiently interact with amyloid protein/peptide, offering enhanced performance in inhibiting amyloid fibrillation and dissolving amyloid fibrils. Our results imply that nanoparticle‐based artificial molecular chaperones may offer a promising therapeutic approach to combat neurodegenerative disease. 相似文献
7.
Reinhard I. Boysen 《Journal of separation science》2019,42(1):51-71
This review documents recent advances in the design, synthesis, characterization, and application of molecularly imprinted polymers in the form of monoliths and particles/beads for the use in the separation and analysis of proteins with solid‐phase extraction or liquid chromatography. The merits of three‐dimensional molecular imprinting, whereby the molecular template is randomly embedded in the polymer, and two‐dimensional imprinting, in which the template is confined to the surface, are described. Target protein binding can be achieved by either using the entire protein as a template or by using a protein substructure as template, that is, a peptide, as in the "epitope" approach. The intended approach and strategy then determine the choice of polymerization method. A synopsis has been provided on methods used for the physical, chemical, and functional characterizations and associated performance evaluations of molecularly imprinted and nonimprinted control polymers, involving a diverse range of analytical techniques commonly used for low and high molecular mass analytes. Examples of recent applications demonstrate that, due to the versatility of imprinting methods, molecularly imprinted monoliths or particles/beads can be adapted to protein extraction/depletion and separation procedures relevant to, for example, protein biomarker detection and quantification in biomedical diagnostics and targeted proteomics. 相似文献
8.
Epitope Targeting of Tertiary Protein Structure Enables Target‐Guided Synthesis of a Potent In‐Cell Inhibitor of Botulinum Neurotoxin
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Blake Farrow Michelle Wong Jacquie Malette Dr. Bert Lai Dr. Kaycie M. Deyle Dr. Samir Das Dr. Arundhati Nag Dr. Heather D. Agnew Prof. James R. Heath 《Angewandte Chemie (International ed. in English)》2015,54(24):7114-7119
Botulinum neurotoxin (BoNT) serotype A is the most lethal known toxin and has an occluded structure, which prevents direct inhibition of its active site before it enters the cytosol. Target‐guided synthesis by in situ click chemistry is combined with synthetic epitope targeting to exploit the tertiary structure of the BoNT protein as a landscape for assembling a competitive inhibitor. A substrate‐mimicking peptide macrocycle is used as a direct inhibitor of BoNT. An epitope‐targeting in situ click screen is utilized to identify a second peptide macrocycle ligand that binds to an epitope that, in the folded BoNT structure, is active‐site‐adjacent. A second in situ click screen identifies a molecular bridge between the two macrocycles. The resulting divalent inhibitor exhibits an in vitro inhibition constant of 165 pM against the BoNT/A catalytic chain. The inhibitor is carried into cells by the intact holotoxin, and demonstrates protection and rescue of BoNT intoxication in a human neuron model. 相似文献
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Dr. Samir Das Dr. Arundhati Nag JingXin Liang Dr. David N. Bunck Dr. Aiko Umeda Blake Farrow Matthew B. Coppock Deborah A. Sarkes Amethist S. Finch Heather D. Agnew Suresh Pitram Bert Lai Mary Beth Yu Dr. A. Katrine Museth Dr. Kaycie M. Deyle Bianca Lepe Frances P. Rodriguez‐Rivera Amy McCarthy Belen Alvarez‐Villalonga Ann Chen John Heath Dimitra N. Stratis‐Cullum Prof. James R. Heath 《Angewandte Chemie (International ed. in English)》2015,54(45):13219-13224
We describe a general synthetic strategy for developing high‐affinity peptide binders against specific epitopes of challenging protein biomarkers. The epitope of interest is synthesized as a polypeptide, with a detection biotin tag and a strategically placed azide (or alkyne) presenting amino acid. This synthetic epitope (SynEp) is incubated with a library of complementary alkyne or azide presenting peptides. Library elements that bind the SynEp in the correct orientation undergo the Huisgen cycloaddition, and are covalently linked to the SynEp. Hit peptides are tested against the full‐length protein to identify the best binder. We describe development of epitope‐targeted linear or macrocycle peptide ligands against 12 different diagnostic or therapeutic analytes. The general epitope targeting capability for these low molecular weight synthetic ligands enables a range of therapeutic and diagnostic applications, similar to those of monoclonal antibodies. 相似文献
10.
Peptide Conjugates for Directing the Morphology and Assembly of 1D Nanoparticle Superstructures
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Chen Zhang Dr. Chengyi Song Dr. H. Christopher Fry Prof. Nathaniel L. Rosi 《Chemistry (Weinheim an der Bergstrasse, Germany)》2014,20(4):941-945
Designed peptide conjugates molecules are used to direct the synthesis and assembly of gold nanoparticles into complex 1D nanoparticle superstructures with various morphologies. Four peptide conjugates, each based on the gold‐binding peptide (AYSSGAPPMPPF; PEPAu), are prepared: C12H23O‐AYSSGAPPMPP ( 1 ), C12H23O‐AYSSGAPPMPPF ( 2 ), C12H23O‐AYSSGAPPMPPFF ( 3 ), and C12H23O‐AYSSGAPPMPPFFF ( 4 ). The affect that C‐terminal hydrophobic F residues have on both the soft‐assembly of the peptide conjugates and the resulting assembly of gold nanoparticle superstructures is examined. It is shown that the addition of two C‐terminal F residues ( 3 ) leads to thick, branched 1D gold nanoparticle superstructures, whereas the addition of three C‐terminal F residues ( 4 ) leads to bundling of thin 1D nanoparticle superstructures. 相似文献
11.
Jianhao Wang Zhilan Zhu Wenjing Jia Lin Qiu Yufeng Chang Jie Li Luping Ma Ying You Jianpeng Wang Li Liu Jiang Xia Xiaoqian Liu Yong‐Qiang Li Pengju Jiang 《Electrophoresis》2019,40(7):1019-1026
Despite the numerous techniques developed for the studying nanoparticle and peptide interaction nowadays, sensitive and convenient assay in the process of flow, especially to simulate the self‐assembly of quantum dots (QDs) and peptide inflow in blood vessels, still remains big challenges. Here, we report a novel assay for studying the self‐assembly of QDs and peptide, based on CE using a bending capillary. We demonstrate that the semicircles numbers of the bending capillary affect the self‐assembly kinetics of CdSe/ZnS QDs and ATTO‐D3LVPRGSGP9G2H6 peptide. Moreover, benefitting from this novel assay, the effect of the position on the self‐assembly has also been realized. More importantly, we also demonstrate that this novel assay can be used for studying the stability of the QDs–peptide complex inflow. We believe that our novel assay proposed in this work could be further used as a general strategy for the studying nanoparticle–biomolecule interaction or biomolecule–biomolecule interaction. 相似文献
12.
《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2017,129(31):9126-9130
Interactions between proteins frequently involve recognition sequences based on multivalent binding events. Dimeric 14‐3‐3 adapter proteins are a prominent example and typically bind partner proteins in a phosphorylation‐dependent mono‐ or bivalent manner. Herein we describe the development of a cucurbit[8]uril (Q8)‐based supramolecular system, which in conjunction with the 14‐3‐3 protein dimer acts as a binary and bivalent protein assembly platform. We fused the phenylalanine–glycine–glycine (FGG) tripeptide motif to the N‐terminus of the 14‐3‐3‐binding epitope of the estrogen receptor α (ERα) for selective binding to Q8. Q8‐induced dimerization of the ERα epitope augmented its affinity towards 14‐3‐3 through a binary bivalent binding mode. The crystal structure of the Q8‐induced ternary complex revealed molecular insight into the multiple supramolecular interactions between the protein, the peptide, and Q8. 相似文献
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本工作合成了一种核壳型的抗原决定基磁性分子印迹聚合物,并用于选择性识别目标蛋白细胞色素c(Cytochrome c,Cyt c)。制备过程中先用溶剂热法合成Fe_3O_4磁性纳米粒子,然后加入Cyt c其C端的九肽作为模板,进行一段时间的预组装,最后加入多巴胺盐酸盐(DA)溶液,调节反应体系的p H使多巴胺聚合在磁球表面。洗脱掉模板后,即得到分子印迹聚合物。优化DA的用量使聚合物达到最佳的吸附效果。在最优条件下,制得的印迹聚合物对目标蛋白有较好的吸附选择性,并且有良好的重复利用性。此外,用抗原决定基做模板制得的聚合物的吸附容量和印迹因子明显优于用相应蛋白质做模板的情况。 相似文献
14.
Synthesis of photoactive single‐chain folded polymeric nanoparticles via combination of radical polymerization techniques and Menschutkin click chemistry
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Secil Babaoglu Demet Karaca Balta Gokhan Temel 《Journal of polymer science. Part A, Polymer chemistry》2017,55(12):1998-2003
This contribution reports that synthesis of polystyrene based photoactive polymeric nanoparticles by radical copolymerization and Menschutkin Chemistry methodology. In the first step, poly(styrene‐co‐chloromethyl styrene) was achieved by thermally initiated radical copolymerizations and subsequently copolymers were reacted to commercially available Type II photoiniator (Michler's ketone) in dilute condition in order to achieve intramolecular crosslinked polymeric nanoparticles. After the characterization studies, polymeric nanoparticles were used for free radical photopolymerization of methacrylic formulations to determine the initiation efficiency. Upon UV irradiation, resulting polymeric nanoparticle lost its globular structure by releasing benzophenone part and transformed into linear copolymer analogue. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017 , 55, 1998–2003 相似文献
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本文对二维蛋白质分子印迹进行了综述:介绍了二维蛋白分子印迹的基本概念;阐述了常见二维蛋白质分子印迹方法的基本原理,包括表位印迹法、溶胶-凝胶法、射频光电等离子沉积法和Langmuir单层法等;根据二维蛋白分子印迹材料的不同形式,详细叙述了二维蛋白质分子印迹薄膜、核-壳微球、纳米线、Langmuir脂质体单层的制备过程、结合能力、选择识别性能;分析了目前二维蛋白质分子印迹技术存在的一些不足和进一步研究的方向。 相似文献
16.
Free‐Standing Gold‐Nanoparticle Monolayer Film Fabricated by Protein Self‐Assembly of α‐Synuclein
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Junghee Lee Dr. Ghibom Bhak Dr. Ji‐Hye Lee Woohyun Park Minwoo Lee Dr. Daekyun Lee Prof. Noo Li Jeon Prof. Dae H. Jeong Prof. Kookheon Char Prof. Seung R. Paik 《Angewandte Chemie (International ed. in English)》2015,54(15):4571-4576
Free‐standing nanoparticle films are of great importance for developing future nano‐electronic devices. We introduce a protein‐based fabrication strategy of free‐standing nanoparticle monolayer films. α‐Synuclein, an amyloidogenic protein, was utilized to yield a tightly packed gold‐nanoparticle monolayer film interconnected by protein β‐sheet interactions. Owing to the stable protein–protein interaction, the film was successfully expanded to a 4‐inch diameter sheet, which has not been achieved with any other free‐standing nanoparticle monolayers. The film was flexible in solution, so it formed a conformal contact, surrounding even microspheres. Additionally, the monolayer film was readily patterned at micrometer‐scale and thus unprecedented double‐component nanoparticle films were fabricated. Therefore, the free‐floating gold‐nanoparticle monolayer sheets with these properties could make the film useful for the development of bio‐integrated nano‐devices and high‐performance sensors. 相似文献
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Mussel‐Inspired Protein Nanoparticles Containing Iron(III)–DOPA Complexes for pH‐Responsive Drug Delivery
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Dr. Bum Jin Kim Hogyun Cheong Dr. Byeong Hee Hwang Prof. Hyung Joon Cha 《Angewandte Chemie (International ed. in English)》2015,54(25):7318-7322
A novel bioinspired strategy for protein nanoparticle (NP) synthesis to achieve pH‐responsive drug release exploits the pH‐dependent changes in the coordination stoichiometry of iron(III)–3,4‐dihydroxyphenylalanine (DOPA) complexes, which play a major cross‐linking role in mussel byssal threads. Doxorubicin‐loaded polymeric NPs that are based on FeIII–DOPA complexation were thus synthesized with a DOPA‐modified recombinant mussel adhesive protein through a co‐electrospraying process. The release of doxorubicin was found to be predominantly governed by a change in the structure of the FeIII–DOPA complexes induced by an acidic pH value. It was also demonstrated that the fabricated NPs exhibited effective cytotoxicity towards cancer cells through efficient cellular uptake and cytosolic release. Therefore, it is anticipated that FeIII–DOPA complexation can be successfully utilized as a new design principle for pH‐responsive NPs for diverse controlled drug‐delivery applications. 相似文献
18.
Monodisperse hybrid Janus nanofibers with the structure that one Au nanoparticle (AuNP) is connected to one end of a polymeric nanofiber were prepared by the self‐assembly between polymeric micelles and the tadpole‐like conjugates resulting from one‐to‐one complexation of long DNA chains with AuNPs. 相似文献
19.
Macht M Marquardt A Deininger SO Damoc E Kohlmann M Przybylski M 《Analytical and bioanalytical chemistry》2004,378(4):1102-1111
We describe here a new approach for the identification of affinity-bound proteins by proteolytic generation and mass spectrometric analysis of their antibody bound epitope peptides (epitope excision). The cardiac muscle protein troponin T was chosen as a protein antigen because of its diagnostic importance in myocardial infarct, and its previously characterised epitope structure. Two monoclonal antibodies (IgG1-1B10 and IgG1-11.7) raised against intact human troponin T were found to be completely cross reactive with bovine heart troponin T. A combination of immuno-affinity isolation, partial proteolytic degradation (epitope excision), mass spectrometric peptide mapping, and database analysis was used for the direct identification of Tn T from bovine heart cell lysate. Selective binding of the protein was achieved by addition of bovine heart cell lysate to the Sepharose-immobilised monoclonal antibodies, followed by removal of supernatant material containing unbound protein. While still bound to the affinity matrix the protein was partially degraded thereby generating a set of affinity-bound, overlapping peptide fragments comprising the epitope. Following dissociation from the antibody the epitope peptides were analysed by matrix assisted laser desorption-ionisation (MALDI) and electrospray-ionisation (ESI) mass spectrometry. The peptide masses identified by mass spectrometry were used to perform an automated database search, combined with a search for a common "epitope motif". This procedure resulted in the unequivocal identification of the protein from biological material with only a minimum number of peptide masses, and requiring only limited mass-determination accuracy. The dramatic increase of selectivity for identification of the protein by combining the antigen-antibody specificity with the redundancy of peptide sequences renders this "affinity-proteomics" approach a powerful tool for mass spectrometric identification of proteins from biological material. 相似文献
20.
High Affinity Recognition of a Selected Amino Acid Epitope within a Protein by Cucurbit[8]uril Complexation
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Dr. Silvia Sonzini Dr. Alessio Marcozzi Dr. Raphael J. Gubeli Dr. Christopher F. van der Walle Dr. Peter Ravn Prof. Andreas Herrmann Prof. Oren A. Scherman 《Angewandte Chemie (International ed. in English)》2016,55(45):14000-14004
Supramolecular interactions between the host cucurbit[8]uril (CB[8]) and amino acids have been widely interrogated, but recognition of specific motifs within a protein domain have never been reported. A phage display approach was herein used to select motifs with the highest binding affinity for the heteroternary complex with methyl viologen and CB[8] (MV?CB[8]) within a vast pool of cyclic peptide sequences. From the selected motifs, an epitope consisting of three amino acid was extrapolated and incorporated into a solvent‐exposed loop of a protein domain; the protein exhibited micromolar binding affinity for the MV?CB[8] complex, matching that of the cyclic peptide. By achieving selective CB[8]‐mediated conjugation of a small molecule to a recombinant protein scaffold we pave the way to biomedical applications of this simple ternary system. 相似文献