keyword
MENU ▼
Read by QxMD icon Read
search

Dna-encoded library

keyword
https://www.readbyqxmd.com/read/28318088/twenty-five-years-of-dna-encoded-chemical-libraries
#1
EDITORIAL
Dario Neri
Reference library: The availability of DNA-encoded chemical libraries containing billions of compounds facilitates the discovery of binding molecules for pharmaceutical applications and for investigating biological processes. This Special Issue highlights the use of this library technology and some of the latest developments in the field.
March 20, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28287689/analysis-of-current-dna-encoded-library-screening-data-indicates-higher-false-negative-rates-for-numerically-larger-libraries
#2
Alexander L Satz, Remo Hochstrasser, Ann C Petersen
To optimize future DNA encoded library design, we have attempted to quantify the library size at which signal becomes undetectable. To accomplish this we i) have calculated that percent yields of individual library members following a screen range from 0.002-1%, ii) extrapolated that ~ 1 million copies per library member are required at the outset of a screen, and iii) from this extrapolation predict that false negative rates will begin to outweigh the benefit of increased diversity at library sizes >108...
March 13, 2017: ACS Combinatorial Science
https://www.readbyqxmd.com/read/28287381/a-preliminary-evaluation-of-next-generation-sequencing-as-a-screening-tool-for-targeted-genotyping-of-erythrocyte-and-platelet-antigens-in-blood-donors
#3
Agnieszka Orzińska, Katarzyna Guz, Michał Mikula, Maria Kulecka, Anna Kluska, Aneta Balabas, Monika Pelc-Kłopotowska, Jerzy Ostrowski, Ewa Brojer
BACKGROUND: Matching the compatibility of donor blood with the recipient's antigens prevents alloimmunisation. Next-generation sequencing (NGS) technology is a promising method for extensive blood group and platelet antigen genotyping of blood donors. It circumvents the limitations of detecting known alleles based on predefined polymorphisms and enables targeted sequencing on a massive scale. The aim of this study was to evaluate the NGS AmpliSeq application on the Ion Torrent platform as a screening tool for genotyping blood donors' erythrocyte/platelet antigens...
March 10, 2017: Blood Transfusion, Trasfusione del Sangue
https://www.readbyqxmd.com/read/28281333/discovering-drugs-with-dna-encoded-library-technology-from-concept-to-clinic-with-an-inhibitor-of-soluble-epoxide-hydrolase
#4
Svetlana Belyanskaya, Yun Ding, James Callahan, Aili Lazaar, David Israel
DNA encoded chemical library technology was developed with the vision of becoming a transformational platform for drug discovery. The hope was that a new screening paradigm for low molecular weight drugs would be enabled by combining the vast molecular diversity achievable with combinatorial chemistry, the information encoding attributes of DNA, the power of molecular biology and a streamlined selection-based discovery process. We describe the discovery and early clinical development of GSK2256294, an inhibitor of the enzyme soluble epoxide hydrolase (sEH, EPHX2) using Encoded Library Technology (ELT)...
March 9, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28277838/using-natural-products-for-drug-discovery-the-impact-of-the-genomics-era
#5
Mingzi M Zhang, Qiao Yuan, Ee Lui Ang, Huimin Zhao
Evolutionarily selected over billions of years for their interactions with biomolecules, natural products have been and continue to be a major source of pharmaceuticals. In the 1990s, pharmaceutical companies scaled down their natural product discovery programs in favor of synthetic chemical libraries due to major challenges such as high rediscovery rates, challenging isolation, and low production titers. Propelled by advances in DNA sequencing and synthetic biology technologies, insights into microbial secondary metabolism provided have inspired a number of strategies to address these challenges...
March 4, 2017: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/28276654/a-family-13-thioesterase-isolated-from-an-activated-sludge-metagenome-insights-into-aromatic-compounds-metabolism
#6
Ayixon Sánchez-Reyez, Ramón Alberto Batista-García, Gilberto Valdés-García, Ernesto Ortiz, Lucía Perezgasga, Andrés Zárate-Romero, Nina Pastor, Jorge Luis Folch-Mallol
Activated sludge is produced during the treatment of sewage and industrial wastewaters. Its diverse chemical composition allows growth of a large collection of microbial phylotypes with very different physiologic and metabolic profiles. Thus, activated sludge is considered as an excellent environment to discover novel enzymes through functional metagenomics, especially activities related with degradation of environmental pollutants. Metagenomic DNA was isolated and purified from an activated sludge sample. Metagenomic libraries were subsequently constructed in Escherichia coli...
March 9, 2017: Proteins
https://www.readbyqxmd.com/read/28273103/functional-metagenomics-reveals-novel-%C3%AE-galactosidases-not-predictable-from-gene-sequences
#7
Jiujun Cheng, Tatyana Romantsov, Katja Engel, Andrew C Doxey, David R Rose, Josh D Neufeld, Trevor C Charles
The techniques of metagenomics have allowed researchers to access the genomic potential of uncultivated microbes, but there remain significant barriers to determination of gene function based on DNA sequence alone. Functional metagenomics, in which DNA is cloned and expressed in surrogate hosts, can overcome these barriers, and make important contributions to the discovery of novel enzymes. In this study, a soil metagenomic library carried in an IncP cosmid was used for functional complementation for β-galactosidase activity in both Sinorhizobium meliloti (α-Proteobacteria) and Escherichia coli (γ-Proteobacteria) backgrounds...
2017: PloS One
https://www.readbyqxmd.com/read/28263788/discovery-of-a-novel-oocyte-specific-kr%C3%A3-ppel-associated-box-domain-containing-zinc-finger-protein-required-for-early-embryogenesis-in-cattle
#8
Jacqelyn M Hand, Kun Zhang, Lei Wang, Prasanthi P Koganti, Kristen Mastrantoni, Sandeep K Rajput, Mohamed Ashry, George W Smith, Jianbo Yao
Zinc finger (ZNF) transcription factors interact with DNA through zinc finger motifs and play important roles in a variety of cellular functions including cell growth, proliferation, development, apoptosis, and intracellular signal transduction. One-third of ZNF proteins in metazoans contain a highly conserved N-terminal motif known as the Krüppel-associated box (KRAB) domain, which acts as a potent, DNA-binding dependent transcriptional repression module. Analysis of RNA-Seq data generated from a bovine oocyte cDNA library identified a novel transcript, which encodes a KRAB-containing ZNF transcription factor (named ZNFO)...
March 2, 2017: Mechanisms of Development
https://www.readbyqxmd.com/read/28249011/transposon-insertion-libraries-for-the-characterization-of-mutants-from-the-kiwifruit-pathogen-pseudomonas-syringae-pv-actinidiae
#9
Carl H Mesarich, Jonathan Rees-George, Paul P Gardner, Fatemeh Ashari Ghomi, Monica L Gerth, Mark T Andersen, Erik H A Rikkerink, Peter C Fineran, Matthew D Templeton
Pseudomonas syringae pv. actinidiae (Psa), the causal agent of kiwifruit canker, is one of the most devastating plant diseases of recent times. We have generated two mini-Tn5-based random insertion libraries of Psa ICMP 18884. The first, a 'phenotype of interest' (POI) library, consists of 10,368 independent mutants gridded into 96-well plates. By replica plating onto selective media, the POI library was successfully screened for auxotrophic and motility mutants. Lipopolysaccharide (LPS) biosynthesis mutants with 'Fuzzy-Spreader'-like morphologies were also identified through a visual screen...
2017: PloS One
https://www.readbyqxmd.com/read/28220596/quantitative-pcr-is-a-valuable-tool-to-monitor-performance-of-dna-encoded-chemical-library-selections
#10
Yizhou Li, Gunther Zimmermann, Jörg Scheuermann, Dario Neri
Phage-display libraries and DNA-encoded chemical libraries (DECL) represent useful tools for the isolation of specific binding molecules out of large combinatorial sets of compounds. In both methods, specific binders are recovered at the end of affinity capture procedures, using target proteins of interest immobilized on a solid support. However, while the efficiency of phage-display selections is routinely quantified by counting the phage titer before and after the affinity capture step, no similar quantification procedures have been reported for the characterization of DNA-encoded chemical library selections...
February 21, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28220154/dna-display-of-folded-rna-libraries-enabling-rna-selex-without-reverse-transcription
#11
I S MacPherson, J S Temme, I J Krauss
A method for the physical attachment of folded RNA libraries to their encoding DNA is presented as a way to circumvent the reverse transcription step during systematic evolution of RNA ligands by exponential enrichment (RNA-SELEX). A DNA library is modified with one isodC base to stall T7 polymerase and a 5' "capture strand" which anneals to the nascent RNA transcript. This method is validated in a selection of RNA aptamers against human α-thrombin with dissociation constants in the low nanomolar range. This method will be useful in the discovery of RNA aptamers and ribozymes containing base modifications that make them resistant to accurate reverse transcription...
March 2, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28199790/an-integrated-microfluidic-processor-for-dna-encoded-combinatorial-library-functional-screening
#12
Andrew B MacConnell, Alexander K Price, Brian M Paegel
DNA-encoded synthesis is rekindling interest in combinatorial compound libraries for drug discovery and in technology for automated and quantitative library screening. Here, we disclose a microfluidic circuit that enables functional screens of DNA-encoded compound beads. The device carries out library bead distribution into picoliter-scale assay reagent droplets, photochemical cleavage of compound from the bead, assay incubation, laser-induced fluorescence-based assay detection, and fluorescence-activated droplet sorting to isolate hits...
March 13, 2017: ACS Combinatorial Science
https://www.readbyqxmd.com/read/28197319/structure-based-design-of-non-natural-peptidic-macrocyclic-mcl-1-inhibitors
#13
Jeffrey W Johannes, Stephanie Bates, Carl Beigie, Matthew A Belmonte, John Breen, Shenggen Cao, Paolo A Centrella, Matthew A Clark, John W Cuozzo, Christoph E Dumelin, Andrew D Ferguson, Sevan Habeshian, David Hargreaves, Camil Joubran, Steven Kazmirski, Anthony D Keefe, Michelle L Lamb, Haiye Lan, Yunxia Li, Hao Ma, Scott Mlynarski, Martin J Packer, Philip B Rawlins, Daniel W Robbins, Haidong Shen, Eric A Sigel, Holly H Soutter, Nancy Su, Dawn M Troast, Haiyun Wang, Kate F Wickson, Chengyan Wu, Ying Zhang, Qiuying Zhao, Xiaolan Zheng, Alexander W Hird
Mcl-1 is a pro-apoptotic BH3 protein family member similar to Bcl-2 and Bcl-xL. Overexpression of Mcl-1 is often seen in various tumors and allows cancer cells to evade apoptosis. Here we report the discovery and optimization of a series of non-natural peptide Mcl-1 inhibitors. Screening of DNA-encoded libraries resulted in hit compound 1, a 1.5 μM Mcl-1 inhibitor. A subsequent crystal structure demonstrated that compound 1 bound to Mcl-1 in a β-turn conformation, such that the two ends of the peptide were close together...
February 9, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28161858/wheat-drought-responsive-wxpl-transcription-factors-regulate-cuticle-biosynthesis-genes
#14
Huihui Bi, Sukanya Luang, Yuan Li, Natalia Bazanova, Nikolai Borisjuk, Maria Hrmova, Sergiy Lopato
The cuticle forms a hydrophobic waxy layer that covers plant organs and provides protection from biotic and abiotic stresses. Transcription of genes responsible for cuticle formation is regulated by several types of transcription factors (TFs). Five orthologous to WAX PRODUCTION (WXP1 and WXP2) genes from Medicago truncatula were isolated from a cDNA library prepared from flag leaves and spikes of drought tolerant wheat (Triticum aestivum, breeding line RAC875) and designated TaWXP-like (TaWXPL) genes. Tissue-specific and drought-responsive expression of TaWXPL1D and TaWXPL2B was investigated by quantitative RT-PCR in two Australian wheat genotypes, RAC875 and Kukri, with contrasting glaucousness and drought tolerance...
February 4, 2017: Plant Molecular Biology
https://www.readbyqxmd.com/read/28151659/discovery-of-a-first-in-class-receptor-interacting-protein-1-rip1-kinase-specific-clinical-candidate-gsk2982772-for-the-treatment-of-inflammatory-diseases
#15
Philip A Harris, Scott B Berger, Jae U Jeong, Rakesh Nagilla, Deepak Bandyopadhyay, Nino Campobasso, Carol A Capriotti, Julie A Cox, Lauren Dare, Xiaoyang Dong, Patrick M Eidam, Joshua N Finger, Sandra J Hoffman, James Kang, Viera Kasparcova, Bryan W King, Ruth Lehr, Yunfeng Lan, Lara K Leister, John D Lich, Thomas T MacDonald, Nathan A Miller, Michael T Ouellette, Christina S Pao, Attiq Rahman, Michael A Reilly, Alan R Rendina, Elizabeth J Rivera, Michelle C Schaeffer, Clark A Sehon, Robert R Singhaus, Helen H Sun, Barbara A Swift, Rachel D Totoritis, Anna Vossenkämper, Paris Ward, David D Wisnoski, Daohua Zhang, Robert W Marquis, Peter J Gough, John Bertin
RIP1 regulates necroptosis and inflammation and may play an important role in contributing to a variety of human pathologies, including immune-mediated inflammatory diseases. Small-molecule inhibitors of RIP1 kinase that are suitable for advancement into the clinic have yet to be described. Herein, we report our lead optimization of a benzoxazepinone hit from a DNA-encoded library and the discovery and profile of clinical candidate GSK2982772 (compound 5), currently in phase 2a clinical studies for psoriasis, rheumatoid arthritis, and ulcerative colitis...
February 10, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28130548/allosteric-beta-blocker-isolated-from-a-dna-encoded-small-molecule-library
#16
Seungkirl Ahn, Alem W Kahsai, Biswaranjan Pani, Qin-Ting Wang, Shuai Zhao, Alissa L Wall, Ryan T Strachan, Dean P Staus, Laura M Wingler, Lillian D Sun, Justine Sinnaeve, Minjung Choi, Ted Cho, Thomas T Xu, Gwenn M Hansen, Michael B Burnett, Jane E Lamerdin, Daniel L Bassoni, Bryant J Gavino, Gitte Husemoen, Eva K Olsen, Thomas Franch, Stefano Costanzi, Xin Chen, Robert J Lefkowitz
The β2-adrenergic receptor (β2AR) has been a model system for understanding regulatory mechanisms of G-protein-coupled receptor (GPCR) actions and plays a significant role in cardiovascular and pulmonary diseases. Because all known β-adrenergic receptor drugs target the orthosteric binding site of the receptor, we set out to isolate allosteric ligands for this receptor by panning DNA-encoded small-molecule libraries comprising 190 million distinct compounds against purified human β2AR. Here, we report the discovery of a small-molecule negative allosteric modulator (antagonist), compound 15 [([4-((2S)-3-(((S)-3-(3-bromophenyl)-1-(methylamino)-1-oxopropan-2-yl)amino)-2-(2-cyclohexyl-2-phenylacetamido)-3-oxopropyl)benzamide], exhibiting a unique chemotype and low micromolar affinity for the β2AR...
February 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28127897/cell-free-translational-screening-of-an-expression-sequence-tag-library-of-clonorchis-sinensis-for-novel-antigen-discovery
#17
Devi Kasi, Christy Catherine, Seung-Won Lee, Kyung-Ho Lee, Yu Jung Kim, Myeong Ro Lee, Jung Won Ju, Dong-Myung Kim
The rapidly evolving cloning and sequencing technologies have enabled understanding of genomic structure of parasite genomes, opening up new ways of combatting parasite-related diseases. To make the most of the exponentially accumulating genomic data, however, it is crucial to analyze the proteins encoded by these genomic sequences. In this study, we adopted an engineered cell-free protein synthesis system for large-scale expression screening of an expression sequence tag (EST) library of Clonorchis sinensis to identify potential antigens that can be used for diagnosis and treatment of clonorchiasis...
January 27, 2017: Biotechnology Progress
https://www.readbyqxmd.com/read/28127867/application-of-biocatalysis-to-on-dna-carbohydrate-library-synthesis
#18
Baptiste Thomas, Xiaojie Lu, William Birmingham, Kun Huang, Peter Both, Juana Reyes Martinez, Robert Young, Christopher Davie, Sabine Flitsch
DNA-encoded libraries are increasingly used for the discovery of bioactive lead compounds in high-throughput screening programmes against specific biological targets. Although a number of libraries are now available, they cover limited chemical space due to bias in ease of synthesis and the lack of chemical reactions that are compatible with DNA-tagging. For example, compound libraries rarely contain complex biomolecules such as carbohydrates with high level of functionality, stereochemistry and hydrophilicity...
January 26, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28094476/dna-encoded-compound-libraries-as-open-source-a%C3%A2-powerful-pathway-to-new-drugs
#19
EDITORIAL
Richard A Lerner, Sydney Brenner
"… We envisioned an iterative system where a unique DNA tag identifier that encoded the event was appended to each newly formed molecule. These vast collections of molecules are known today as DNA- encoded chemical libraries (DECLs), and allow scientists to do selections on the benchtop that previously required access to large and complex high-throughput screening centers …" Read more in the Guest Editorial by Richard A. Lerner and Sydney Brenner.
January 24, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28067010/hit-validation-methodologies-for-ligands-isolated-from-dna-encoded-chemical-libraries
#20
Gunther Zimmermann, Yizhou Li, Ulrike Rieder, Martin Mattarella, Dario Neri, Jörg Scheuermann
DNA-encoded chemical libraries (DECLs) are large collections of compounds linked to DNA fragments, serving as amplifiable barcodes, which can be screened on target proteins of interest. In typical DECL selections, preferential binders are identified by high-throughput DNA sequencing, comparing their frequency before and after the affinity capture step. Hits identified in this procedure need to be confirmed, by resynthesis and by performing affinity measurements. In this article, we present novel methods, based on the hybridization of oligonucleotide conjugates with fluorescently-labeled complementary oligonucleotides, which facilitate the determination of affinity constants and kinetic dissociation constants...
January 9, 2017: Chembiochem: a European Journal of Chemical Biology
keyword
keyword
109708
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"