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Bioconjugate Chemistry

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https://www.readbyqxmd.com/read/28228012/investigation-of-thermally-induced-cellular-ablation-and-heat-response-triggered-by-planar-mos2-based-nanocomposite
#1
Shinya Ariyasu, Jing Mu, Xiao Zhang, Ying Huang, Edwin K L Yeow, Hua Zhang, Bengang Xing
In comparison to conventional tumor treatment methods, photothermal therapy (PTT) is one of the innovative therapeutic strategies that employs light to produce the localized heat for targeted ablation of cancer cells. Among various kinds of heat generation nanomaterials, transition metal dichalcogenide nanosheets, especially-molybdenum disulfide (MoS2) have recently been investigated as one of the promising PTT candidates because of their strong absorbance in the near-infrared (NIR) tissue transparency window and excellent photothermal conversion capability...
February 23, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28225264/fatty-acid-comprising-lysine-conjugates-anti-mrsa-agents-that-display-in-vivo-efficacy-by-disrupting-biofilms-with-no-resistance-development
#2
Mohini Mohan Konai, Jayanta Haldar
Methicillin-resistant Staphylococcus aureus (MRSA) have developed resistance to antibiotics of last resort such as vancomycin, linezolid and daptomycin. Additionally, their biofilm forming capability has set an alarming situation in the treatment of bacterial infections. Herein we report the potency of fatty acid comprising lysine conjugates as novel anti-MRSA agents, which were not only capable of killing growing planktonic MRSA at low concentration (MIC = 3.1-6.3 µg/mL), but also displayed potent activity against non-dividing stationary phase cells...
February 22, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28225258/nanoparticle-based-discrimination-of-single-nucleotide-polymorphism-in-long-dna-sequences
#3
Maria Sanroman-Iglesias, Charles Lawrie, Luis M Liz-Marzán, Marek Grzelczak
Circulating DNA (ctDNA) and specifically the detection cancer-associated mutations in liquid biopsies promises to revolutionize cancer detection. The main difficulty however is that the length of typical ctDNA fragments (~150 bases) can form secondary structures potentially obscuring the mutated fragment from detection. We show that an assay based on gold nanoparticles (65 nm) stabilized with DNA (Au@DNA) can discriminate single nucleotide polymorphism in clinically-relevant DNA sequences (70-140 bases). The preincubation step was crucial to this process, allowing sequential bridging of Au@DNA, so that single base mutation can be discriminated, down to 100 pM concentration...
February 22, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28222590/a-novel-tumor-pretargeting-system-based-on-complementary-l-configured-oligonucleotides
#4
Maik Schubert, Ralf Bergmann, Christian Foerster, Wiebke Sihver, Stefan Vonhoff, Sven Klussmann, Lucas Bethge, Martin Walther, Jörn Schlesinger, Jens Pietzsch, Jörg Steinbach, Hans-Juergen Pietzsch
Unnatural mirror image L-configured oligonucleotides (L-ONs) are a convenient substance class for the application as complementary in vivo recognition system between a tumor specific antibody and a smaller radiolabeled effector molecule in pretargeting approaches. The high hybridization velocity and defined melting conditions are excellent preconditions of the L-ON based methodology. Their high metabolic stability and negligible unspecific binding to endogenous targets are superior characteristics in comparison to their D-configured analogs...
February 22, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28221765/design-of-macroscopically-ordered-liquid-crystalline-hydrogel-columns-knitted-with-nanosilver-for-topical-applications
#5
Sudha Janardhanan Devaki, Reshma Lali Raveendran, Nishanth Kumar Sasidharan
Design of liquid crystalline hydrogels knitted with silver nanoparticles in macroscopic ordering are becoming subject of research interest due to their promising multifunctional applications in biomedical and opto-electronic applications. The present work describes the development of liquid crystalline Schiff-based hydrogel decorated with silver nanoparticles and demonstration of its antifungal applications. Schiff base was prepared from polyglucanaldehyde and chitosan and the former was prepared by the oxidation of amylose (polyglucopyranose) isolated from abundantly available unutilised jackfruit seed starch...
February 21, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28212596/site-specific-dual-functionalization-of-cysteine-residue-in-peptides-and-proteins-with-2-azidoacrylates
#6
Shinya Ariyasu, Hirohito Hayashi, Bengang Xing, Shunsuke Chiba
Herein, we report use of 2-azidoacrylates to perform site-specific dual functionalization of the cysteine residue of peptides and bovine serum albumin (BSA), a native protein containing one free cysteine residue. The sulfhydryl group of the cysteine residue could be conjugated with 2-azidoacrylates bearing various functionalities, such as fluorescent dyes under physiological aqueous buffer conditions, to afford peptide and protein conjugates anchoring an azide moiety. Successive azide-alkyne cycloaddition enables installation of the second functionality, thus affording dual-functionalized peptide- and protein-based materials...
February 21, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28192990/dual-stimuli-activatable-oxidative-stress-amplifying-agent-as-a-hybrid-anticancer-prodrug
#7
Eunji Han, Byeongsu Kwon, Donghyuck Yoo, Changsun Kang, Gilson Khang, Dongwon Lee
Compared to normal cells, cancer cells have a higher level of reactive oxygen species (ROS) due to aberrant metabolism and disruption of redox homeostasis which drive their proliferation and promote progression and metastasis of cancers. The altered redox balance and biological difference between normal cells and cancer cells provide a basis for the development of anticancer agents which are able to generate pharmacological ROS insults to kill cancer cells preferentially. In this study, we report a new hybrid anticancer drug, termed OSamp, which undergoes esterase- and acid-catalyzed hydrolysis to deplete antioxidant glutathione (GSH) and generate ROS, simultaneously...
February 21, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28166625/indocyanine-green-labeled-polysarcosine-for-in-vivo-photoacoustic-tumor-imaging
#8
Kohei Sano, Manami Ohashi, Kengo Kanazaki, Akira Makino, Ning Ding, Jun Deguchi, Yuko Kanada, Masahiro Ono, Hideo Saji
Photoacoustic (PA) imaging has been considered an attractive imaging modality for sensitive and in-depth imaging of biomolecules with a high resolution in vivo. PA imaging probes utilizing fluorescence dyes, including indocyanine green (ICG), have been proposed to enhance PA signal intensity. On the other hand, nanomicelles modified with polysarcosine (PSar), a biocompatible hydrophilic polymer, on their surface have previously achieved rapid tumor uptake, suggesting active transport of PSar into tumor tissues...
February 21, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28215090/nonviral-genome-editing-based-on-a-polymer-derivatized-crispr-nanocomplex-for-targeting-bacterial-pathogens-and-antibiotic-resistance
#9
Yoo Kyung Kang, Kyu Kwon, Jea Sung Ryu, Ha Neul Lee, Chankyu Park, Hyun Jung Chung
The overuse of antibiotics plays a major role in the emergence and spread of multidrug-resistant bacteria. A molecularly targeted, specific treatment method for bacterial pathogens can prevent this problem by reducing the selective pressure during microbial growth. Herein, we introduce a nonviral treatment strategy delivering genome editing material for targeting antibacterial resistance. We apply the CRISPR-Cas9 system, which has been recognized as an innovative tool for highly specific and efficient genome engineering in different organisms, as the delivery cargo...
February 19, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28209057/saturated-fatty-acid-analogues-of-cell-penetrating-peptide-pepfect14-role-of-fatty-acid-modification-in-complexation-and-delivery-of-splice-correcting-oligonucleotides
#10
Tõnis Lehto, Luis Vasconcelos, Helerin Margus, Ricardo Figueroa, Margus Pooga, Mattias Hällbrink, Ulo Langel
Modifying cell-penetrating peptides (CPPs) with fatty acids has long been used to improve peptide-mediated nucleic acid delivery. In this study we have revisited this phenomenon with a systematic approach where we developed a structure-activity relationship to describe the role of the acyl chain length in the transfection process. For that we took a well-studied CPP, PepFect14, as the basis and varied its N-terminal acyl chain length from 2 to 22 carbons. To evaluate the delivery efficiency, the peptides were non-covalently complexed with a splice-correcting oligonucleotide (SCO) and tested in the HeLa pLuc705 reporter cell line...
February 17, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28192992/protein-adsorbed-magnetic-nanoparticle-mediated-assay-for-rapid-detection-of-bacterial-antibiotic-resistance
#11
Taku A Cowger, Yaping Yang, David E Rink, Trever Todd, Hongmin Chen, Ye Shen, Yajun Yan, Jin Xie
Antibiotic susceptibility tests have been used for years as a crucial diagnostic tool against antibiotic-resistant bacteria. However, due to a lack of biomarkers specific to resistant types, these approaches are often time-consuming, inaccurate, and inflexible in drug selections. Here, we present a novel susceptibility test method named protein-adsorbed nanoparticle-mediated matrix-assisted laser desorption-ionization mass spectrometry, or PANMS. Briefly, we adsorb five different proteins (β-casein, α-lactalbumin, human serum albumin, fibrinogen, and avidin) onto the surface of Fe3O4...
February 17, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28122451/mimicking-tumors-toward-more-predictive-in-vitro-models-for-peptide-and-protein-conjugated-drugs
#12
Dirk van den Brand, Leon F Massuger, Roland Brock, Wouter P R Verdurmen
Macromolecular drug candidates and nanoparticles are typically tested in 2D cancer cell culture models, which are often directly followed by in vivo animal studies. The majority of these drug candidates, however, fail in vivo. In contrast to classical small-molecule drugs, multiple barriers exist for these larger molecules that two-dimensional approaches do not recapitulate. In order to provide better mechanistic insights into the parameters controlling success and failure and due to changing ethical perspectives on animal studies, there is a growing need for in vitro models with higher physiological relevance...
February 17, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28208017/tailoring-cellular-uptake-and-fluorescence-of-poly-2-oxazoline-based-nanogels
#13
Ulrich S Schubert, Matthias Hartlieb, Tanja Bus, Joachim Kübel, David Pretzel, Stephanie Hoeppener, Meike N Leiske, Kristian Kempe, Benjamin Dietzek
Controlling the size and charge of nanometer sized objects is of upmost importance for their interactions with cells. We herein present the synthesis of poly(2-oxazoline) based nanogels comprising a hydrophilic shell and an amine containing core compartment. Amine groups were cross-linked using glutaraldehyde resulting in imine based nanogels. As a drug model, amino fluorescein was covalently immobilized within the core, quenching excessive aldehyde functions. By varying the amount of cross-linker, the zeta potential and, hence, the cellular uptake could be adjusted...
February 16, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28205434/recent-advances-on-magnetic-relaxation-switching-assay-based-nanosensors
#14
Yang Zhang, Hong Yang, Zhiguo Zhou, Kai Huang, Shi-Ping Yang, Gang Han
Magnetic relaxation switching assay (MRSw)-based nanosensors respond to the changes of transverse relaxation time (T2) of water molecules resulted from the analyte-induced aggregation / disaggregation of magnetic nanoparticles (MNPs). This strategy has been widely applied to the detections of various substrates from heavy metal ions to organic pollutants, proteins, nucleic acids, bacteria/viruses, and specific cells. Compared with other nanosensors, MRSw-based nanosensors not only are free from the background interferences, signal bleaching, and quenching but also overcome light scattering from samples without pre-treatments...
February 16, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28201871/a-targeted-contrast-agent-specific-to-an-oncoprotein-in-tumor-microenvironment-with-the-potential-for-detection-and-risk-stratification-of-prostate-cancer-with-mri
#15
Zheng Han, Yajuan Li, Sarah Roelle, Zhuxian Zhou, Yuchi Liu, Rob Sabatelle, Aidan DeSanto, Xin Yu, Hui Zhu, Cristina Magi-Galluzzi, Zheng-Rong Lu
Accurate detection and risk stratification are paramount to the clinical management of prostate cancer. Current diagnostic methods, including prostate specific antigen (PSA) screening, are unable to differentiate high-risk tumors from low-risk tumors, resulting in overdiagnosis and overtreatment of numerous patients. A peptide targeted contrast agent, ZD2-Gd(HP-DO3A), specific to an oncoprotein in tumor microenvironment, EDB-FN, was synthesized for non-invasive detection and characterization of aggressive prostate cancer...
February 16, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28201868/enzyme-responsive-liposomes-for-the-delivery-of-anticancer-drugs
#16
Farnaz Fouladi, Kristine J Steffen, Sanku Mallik
Liposomes are nanocarriers that deliver the payloads at the target site, leading to therapeutic drug concentrations at the diseased site and reduced toxic effects in healthy tissues. Several approaches have been used to enhance the ability of the nanocarrier to target the specific tissues, including ligand-targeted liposomes and stimuli-responsive liposomes. Ligand-targeted liposomes exhibit higher uptake by the target tissue due to the targeting ligand attached to the surface, while, the stimuli-responsive liposomes do not release their cargo unless they expose to an endogenous or exogenous stimulant at the target site...
February 16, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28158945/f%C3%A3-rster-resonance-energy-transfer-paired-hydrogel-forming-silk-elastin-like-recombinamers-by-recombinant-conjugation-of-fluorescent-proteins
#17
Arturo Ibáñez-Fonseca, Matilde Alonso, Francisco Javier Arias, José Carlos Rodríguez-Cabello
In the last decades, recombinant structural proteins have become very promising in addressing different issues such as the lack of traceability of biomedical devices or the design of more sensitive biosensors. Among them, we find elastin-like recombinamers (ELRs), which can be designed to self-assemble into diverse structures, such as hydrogels. Furthermore, they might be combined with other protein polymers, such as silk, to give silk-elastin-like recombinamers (SELRs), holding the properties of both proteins...
February 15, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28156100/a-broadly-applicable-assay-for-rapidly-and-accurately-quantifying-dna-surface-coverage-on-diverse-particles
#18
Haixiang Yu, Xiaowen Xu, Pingping Liang, Kang Yong Loh, Bhargav Guntupalli, Daniel Roncancio, Yi Xiao
DNA-modified particles are used extensively for applications in sensing, material science, and molecular biology. The performance of such DNA-modified particles is greatly dependent on the degree of surface coverage, but existing methods for quantitation can only be employed for certain particle compositions and/or conjugation chemistries. We have developed a simple and broadly applicable exonuclease III (Exo III) digestion assay based on the cleavage of phosphodiester bonds-a universal feature of DNA-modified particles-to accurately quantify DNA probe surface coverage on diverse, commonly used particles of different compositions, conjugation chemistries, and sizes...
February 15, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28191958/specific-ligation-of-two-multimeric-enzymes-with-native-peptides-and-immobilization-with-controlled-molar-ratio
#19
Kun Du, Jinjin Zhao, Jian Sun, Wei Feng
D-amino acid oxidases (DAAOs) are flavor enzymes and have been used in resolution of racemic amino acids and manufacturing of pharmaceuticals. However, the evolved H2O2 during the catalysis has deleterious and inhibitory effects. Decomposition of the hydrogen peroxide by catalase (CAT) can eliminate the negative effects. DAAO and CAT are dimeric and tetrameric proteins, respectively. Here the N-terminus of the DAAO subunits has been specifically ligated to the C-terminus of the CAT subunits with native peptides through intein-mediated in vivo protein splicing...
February 13, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28191937/a-versatile-platform-for-the-synthesis-of-orthogonally-cleavable-heteromultifunctional-crosslinkers
#20
Michelle R Sorkin, Joshua A Walker, Joseph S Brown, Christopher A Alabi
Cleavable and heteromultifunctional crosslinkers have proven critical in a wide range of biological applications. Traditional approaches for synthesizing these linkers suffer from various synthetic and functional limitations. In this work, an efficient sequence-defined synthetic methodology, developed for the assembly of oligothioetheramides, was used to address many of these limitations. Four heterotrifunctional crosslinkers with up to two orthogonal internal cleavage sites were synthesized. These linkers were conjugated to a pair of fluorophores that undergo Förster resonance energy transfer (FRET) and a model protein - human transferrin...
February 13, 2017: Bioconjugate Chemistry
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