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https://www.readbyqxmd.com/read/28231426/engineering-of-anti-cd133-tri-specific-molecule-capable-of-inducing-nk-expansion-and-driving-antibody-dependent-cell-mediated-cytotoxicity-adcc
#1
Jörg U Schmohl, Martin Felices, Felix Oh, Alexander J Lenvik, Aaron M Lebeau, Jayanth Panyam, Jeffrey S Miller, Daniel A Vallera
Purpose: The selective elimination of cancer stem cells (CSCs) in tumor patients is a crucial goal because CSCs cause drug refractory relapse. To improve the current conventional bispecific immune-engager platform, a 16133 BiKE, consisting of scFvs binding FcγRIII (CD16) on NK cells and CD133 on carcinoma cells, was first synthesized and a modified IL-15 crosslinker capable of stimulating NK effector cells was introduced. Materials and Methods: DNA shuffling and ligation techniques were used to assemble and synthesize the 1615133 trispecific NK cell engager (TriKE)...
February 20, 2017: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/28230996/a-facile-n-mercaptoethoxyglycinamide-mega-linker-ap-proach-to-peptide-thioesterification-and-cyclization
#2
Patrick M M Shelton, Caroline E Weller, Champak Chatterjee
The C-terminal selective electrophilic activation of polypeptides is essential for site-specific peptide mod-ification and conjugation techniques such as Native Chemi-cal Ligation (NCL). Peptide C-terminal α-thioesters are par-ticularly valuable precursors for NCL, due to their hydrolytic stability in aqueous buffers and reactivity toward thiol nucle-ophiles. The synthesis of peptide α-thioesters, however, re-quires harsh acidic conditions or complex chemical manipu-lations, which ultimately limits their functional group com-patibility and broad utility...
February 23, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28230992/novel-design-of-heptad-amphiphiles-to-enhance-cell-selectivity-salt-resistance-anti-biofilm-properties-and-their-membrane-disruptive-mechanism
#3
Xiujing Dou, Xin Zhu, Jiajun Wang, Na Dong, Anshan Shan
Coiled-coil, a basic folding pattern of native proteins, was previously demonstrated to be associated with the specific spatial recognition, association, and dissociation of proteins and can be used to perfect engineering peptide model. Thus, in this study, a series of amphiphiles composed of heptads repeats with coiled-coil structures was constructed, and the designed peptides exhibited a broad spectrum of antimicrobial activities. Circular dichroism and biological assays showed that the heptad repeats and length of the linker between the heptads largely influenced the amphiphile's helical propensity and cell selectivity...
February 23, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28230851/using-hiclip-to-identify-rna-duplexes-that-interact-with-a-specific-rna-binding-protein
#4
Yoichiro Sugimoto, Anob M Chakrabarti, Nicholas M Luscombe, Jernej Ule
The structure of RNA molecules has a critical role in regulating gene expression, largely through influencing their interactions with RNA-binding proteins (RBPs). RNA hybrid and individual-nucleotide resolution UV cross-linking and immunoprecipitation (hiCLIP) is a transcriptome-wide method of monitoring these interactions by identifying RNA duplexes bound by a specific RBP. The hiCLIP protocol consists of the following steps: in vivo cross-linking of RBPs to their bound RNAs; partial RNA digestion and purification of RNA duplexes interacting with the specific RBP using immunoprecipitation; ligation of the two arms of RNA duplexes via a linker; reverse transcription; cDNA library amplification; and finally high-throughput DNA sequencing...
March 2017: Nature Protocols
https://www.readbyqxmd.com/read/28229535/enrichment-and-viability-inhibition-of-circulating-tumor-cells-on-a-dual-acid-responsive-composite-nanofiber-film
#5
Wenqian Wang, Yaya Cheng, Yansheng Li, Hao Zhou, Li-Ping Xu, Yongqiang Wen, Liang Zhao, Xueji Zhang
The formation and metastatic colonization of circulating tumor cells (CTCs) are responsible for the vast majority of cancer-related deaths. Over the last decade, drug delivery system (DDS) has been rapidly developed with nanotechnology arising, however, most of the reported tumor-targeting DDSs were just able to deliver drugs to the solid tumor cells but not CTCs. In here, a novel drug delivery system was constructed with composite nanofiber film to inhibit the viability of circulating tumor cells (CTCs). In this system, gold nanoparticles (Au NPs) were functionalized with doxorubicin (DOX) through an acid-responsive cleavable linker to get the Au-DOX NPs...
February 23, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28229133/towards-enhanced-optical-sensor-performance-seira-and-sers-with-plasmonic-nanostars
#6
O Bibikova, J Haas, A I López-Lorente, A Popov, M Kinnunen, I Meglinski, B Mizaikoff
We report the preparation and characterization of plasmonic chip-based systems comprising self-assembled gold nanostars at silicon substrates that enable concomitantly enhanced Raman (surface enhanced Raman spectroscopy; SERS) and mid-infrared (surface enhanced infrared reflection or absorption spectroscopy; SEIRA) spectral signatures. The high-aspect-ratio structure of gold nanostars provides an increased number of hot spots at their surface, which results in an electric field enhancement around the nanomaterial...
February 23, 2017: Analyst
https://www.readbyqxmd.com/read/28228322/anti-tumour-research-of-recombinant-bcg-using-bzlf1-and-hgm-csf-fusion-genes
#7
Qing-Jie Xue, Yun-Qing Li, Chun-Qing Yang, Ting Chen, Xiu-Zhen Li, Baohua Cheng, Chun-Mei Wang
The random primer Oligo(dT)15 was used in RT-PCR to obtain cDNA from the human granulocyte macrophage colony stimulating factor (hGM-CSF) gene and the Epstein-Barr virus (EBV) gene BZLF1. Then, the sequence splicing overlap extension method was used to obtain a GCBF fusion gene containing a linker sequence that encoded the polypeptide (Gly4Ser)3. The GCBF fusion gene was inserted into pMV261, which was then transformed into competent E. coli DH5 alpha cells, and positive cells were selected based on kanamycin resistance on LB plates...
February 19, 2017: Vaccine
https://www.readbyqxmd.com/read/28226280/development-of-electrochemical-biosensor-for-detection-of-pathogenic-microorganism-in-asian-dust-events
#8
Min-Sang Yoo, Minguk Shin, Younghun Kim, Min Jang, Yoon-E Choi, Si Jae Park, Jonghoon Choi, Jinyoung Lee, Chulhwan Park
We developed a single-walled carbon nanotubes (SWCNTs)-based electrochemical biosensor for the detection of Bacillus subtilis, one of the microorganisms observed in Asian dust events, which causes respiratory diseases such as asthma and pneumonia. SWCNTs plays the role of a transducer in biological antigen/antibody reaction for the electrical signal while 1-pyrenebutanoic acid succinimidyl ester (1-PBSE) and ant-B. subtilis were performed as a chemical linker and an acceptor, respectively, for the adhesion of target microorganism in the developed biosensor...
February 19, 2017: Chemosphere
https://www.readbyqxmd.com/read/28225867/investigating-ego-modules-and-pathways-in-osteosarcoma-by-integrating-the-egonet-algorithm-and-pathway-analysis
#9
X Y Chen, Y H Chen, L J Zhang, Y Wang, Z C Tong
Osteosarcoma (OS) is the most common primary bone malignancy, but current therapies are far from effective for all patients. A better understanding of the pathological mechanism of OS may help to achieve new treatments for this tumor. Hence, the objective of this study was to investigate ego modules and pathways in OS utilizing EgoNet algorithm and pathway-related analysis, and reveal pathological mechanisms underlying OS. The EgoNet algorithm comprises four steps: constructing background protein-protein interaction (PPI) network (PPIN) based on gene expression data and PPI data; extracting differential expression network (DEN) from the background PPIN; identifying ego genes according to topological features of genes in reweighted DEN; and collecting ego modules using module search by ego gene expansion...
February 16, 2017: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/28225082/environmentally-friendly-chitosan-pei-grafted-magnetic-gelatin-for-the-highly-effective-removal-of-heavy-metals-from-drinking-water
#10
Bingbing Li, Feng Zhou, Kai Huang, Yipei Wang, Surong Mei, Yikai Zhou, Tao Jing
The development of environmentally friendly sorbents with a high adsorption capacity is an essential problem in the removal of heavy metals from drinking water. In this study, magnetic gelatin was prepared using transglutaminase as a cross-linker, which could only catalyze an acyl-transfer reaction between lysine and glutamine residues of the gelatin and not affect other amino groups. Therefore, it was beneficial for the further modification based on the amino groups, and did not affect the spatial structure of gelatin, which can effectively prevent the embedding of active sites in the polymer matrix...
February 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28224143/ara-h-2-cross-linking-catalyzed-by-mtgase-decreases-its-allergenicity
#11
Zhihua Wu, Jun Lian, Ruifang Zhao, Kun Li, Xin Li, Anshu Yang, Ping Tong, Hongbing Chen
Peanuts, whose major allergen is Ara h 2, are included among the eight major food allergens. After reduction using dithiothreitol (DTT), cross-linking of Ara h 2 could be catalyzed by microbial transglutaminase (MTGase), a widely used enzyme in the food industry. In this study, Ara h 2 cross-linking was catalyzed by MTGase after it was reduced by DTT. Using mass spectrometry and PLINK software, five cross-linkers were identified, and five linear allergen epitopes were found to be involved in the reactions. The IgE binding capacity of cross-linked Ara h 2 was found to be significantly lower compared to that of native and reduced Ara h 2...
February 22, 2017: Food & Function
https://www.readbyqxmd.com/read/28223423/modulating-therapeutic-activity-and-toxicity-of-pyrrolobenzodiazepine-antibody-drug-conjugates-with-self-immolative-disulfide-linkers
#12
Thomas H Pillow, Melissa Schutten, Shang-Fan Yu, Rachana Ohri, Jack Sadowsky, Kirsten Achilles Poon, Willy Solis, Fiona Zhong, Geoffrey Del Rosario, Mary Ann T Go, Jeffery Lau, Sharon Yee, Jintang He, Luna Liu, Carl Ng, Keyang Xu, Douglas D Leipold, Amrita V Kamath, Donglu Zhang, Luke Masterson, Stephen J Gregson, Philip W Howard, Fan Fang, Jinhua Chen, Janet Gunzner-Toste, Katherine K Kozak, Susan Spencer, Paul Polakis, Andrew G Polson, John A Flygare, Jagath R Junutula
A novel disulfide linker was designed to enable a direct connection between cytotoxic pyrrolobenzodiazepine (PBD) drugs and the cysteine on a targeting antibody for use in antibody-drug conjugates (ADCs). ADCs composed of a cysteine-engineered antibody were armed with a PBD using a self-immolative disulfide linker. Both the chemical linker and the antibody site were optimized for this new bioconjugation strategy to provide a highly stable and efficacious ADC. This novel disulfide ADC was compared to a conjugate containing the same PBD drug, but attached to the antibody via a peptide linker...
February 21, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28223020/synthesis-and-evaluation-of-prodrugs-of-corticotropin-releasing-factor-1-crf1-receptor-antagonist-bms-665053-leading-to-improved-oral-bioavailability
#13
Richard A Hartz, Vivekananda M Vrudhula, Vijay T Ahuja, James E Grace, Nicholas J Lodge, Joanne J Bronson, John E Macor
A series of phosphate and ester-based prodrugs of anilinopyrazinone 1 (BMS-665053) containing either a methylene or an (acyloxy)alkoxy linker was prepared and evaluated in rat pharmacokinetic studies with the goal of improving the oral bioavailability of the parent (1). The prodrugs, in general, had improved aqueous solubility and oral bioavailability compared to 1. Prodrug 12, which contains an (acyloxy)alkoxy linker, showed the greatest improvement in the oral bioavailability relative to the parent (1), with a seven-fold increase (from 5% to 36%) in rat pharmacokinetic studies...
February 10, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28222617/presynaptic-calmodulin-targets-lessons-from-structural-proteomics
#14
Noa Lipstein, Melanie Göth, Christine Piotrowski, Kevin Pagel, Andrea Sinz, Olaf Jahn
Calmodulin (CaM) is a highly conserved Ca(2+)-binding protein that is exceptionally abundant in the brain. In the presynaptic compartment of neurons, CaM transduces changes in Ca(2+) concentration into the regulation of synaptic transmission dynamics. Areas covered: We review selected literature including published CaM interactor screens and outline established and candidate presynaptic CaM targets. We present a workflow of biochemical and structural proteomic methods that were used to identify and characterize the interactions between CaM and Munc13 proteins...
March 2017: Expert Review of Proteomics
https://www.readbyqxmd.com/read/28221380/spatial-mismatch-non-additive-binding-energies-and-selectivity-in-supramolecular-complexes
#15
REVIEW
Hans-Jörg Schneider
The consequences of spatial mismatch between a receptor and ligand on affinity and selectivity of supramolecular complexes are illustrated with several examples. Conformationally rigid complexes and shorter-range non-covalent forces are characterized by large affinity changes, in contrast to more flexible systems. In the most frequent complexes with several spaciously separated binding sites, the additivity of binding energies and the correlation between affinity and selectivity is often lost by partial mismatch...
February 21, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28220925/slow-relaxation-of-the-magnetization-observed-in-an-antiferromagnetically-ordered-phase-for-scm-based-two-dimensional-layered-compounds
#16
Koichi Kagesawa, Yuki Nishimura, Hiroki Yoshida, Brian K Breedlove, Masahiro Yamashita, Hitoshi Miyasaka
Two-dimensional layered compounds with different counteranions, [{Mn(salen)}4C6](BF4)2·2(CH3OH) (1) and [{Mn(salen)}4C6](PF6)2·2(CH3OH) (2) (salen(2-) = N,N'-bis(salicylideneiminato), C6(2-) = C6H12(COO)2(2-)), were synthesized by assembling [Mn(salen)(H2O)]X (X(-) = BF4(-) and PF6(-)) and C6H12(CO2(-))2 (C6(2-)) in a methanol/2-propanol medium. The compounds have similar structures, which are composed of Mn(salen) out-of-plane dimers bridged by μ(4)-type C6(2-) ions, forming a brick-wall-type network of [-{Mn2}-OCO-] chains alternately connected via C6H12 linkers of C6(2-) moieties...
February 21, 2017: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/28220537/immobilization-of-horseradish-peroxidase-on-zno-nanowires-macroporous-sio2-composites-for-the-complete-decolorization-of-anthraquinone-dyes
#17
Huaiyan Sun, Xinyu Jin, Feng Jiang, Ruifeng Zhang
A Zinc Oxide (ZnO) nanowires/ macroporous Silicon dioxide (SiO2 ) composite was used as support to immobilize horseradish peroxidase (HRP) simply by in-situ cross-linking method. As cross-linker was adsorbed on the surface of ZnO nanowires, the cross-linked HRP was quite different from the traditional cross-linking enzyme aggregates (CLEAs) on both structure and catalytic performance. Among three epoxy compounds diethylene glycol diglycidyl ether (DDE) was the best cross-linker, with which the loading amount of HRP with pI of 5...
February 21, 2017: Biotechnology and Applied Biochemistry
https://www.readbyqxmd.com/read/28220502/variations-on-a-nucleosome-theme-the-structural-basis-of-centromere-function
#18
Olga Moreno-Moreno, Mònica Torras-Llort, Fernando Azorín
The centromere is a specialized chromosomal structure that dictates kinetochore assembly and, thus, is essential for accurate chromosome segregation. Centromere identity is determined epigenetically by the presence of a centromere-specific histone H3 variant, CENP-A, that replaces canonical H3 in centromeric chromatin. Here, we discuss recent work by Roulland et al. that identifies structural elements of the nucleosome as essential determinants of centromere function. In particular, CENP-A nucleosomes have flexible DNA ends due to the short αN helix of CENP-A...
February 21, 2017: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
https://www.readbyqxmd.com/read/28220175/a-mechanically-robust-hydrogel-with-thermally-induced-plasticity-and-a-shape-memory-effect
#19
Kang Peng, Hansen Yu, Haiyang Yang, Xiang Hao, Akram Yasin, Xingyuan Zhang
A new class of smart structural hydrogels is prepared by introducing dual cross-linkers into a single-network system. The present hydrogel, on the one hand, exhibits excellent mechanical properties; on the other hand, it exhibits thermally induced plasticity and a shape memory effect without any overlap.
February 21, 2017: Soft Matter
https://www.readbyqxmd.com/read/28220155/specificity-of-snp-detection-with-molecular-beacons-is-improved-by-stem-and-loop-separation-with-spacers
#20
Valentina M Farzan, Mikhail L Markelov, Alexander Yu Skoblov, German A Shipulin, Timofei S Zatsepin
Molecular beacons (MBs) are valuable tools in molecular biology, clinical diagnostics and analytical chemistry. Here we describe a novel approach for the design of MBs with nucleotide or non-nucleotide linkers between the stem and loop regions. Such modified MBs have significantly improved specificity and performance for single nucleotide polymorphism (SNP) detection. These advantages are especially distinct, when compared to the classic MBs, in the case of possible interactions between the stem and loop regions...
February 21, 2017: Analyst
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