Synthetic antibody technologies

Adams, Jarrett; Sidhu, Sachdev S.

doi:10.1016/j.sbi.2013.11.003

Cited by 61 publications

(46 citation statements)

References 55 publications

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“…Miniature proteins consisting of helical bundles, β-sheet barrels, and loops, along with synthetic antibodies[105-109] are now routinely used to enrich ligands for protein targets, especially for extracellular receptors. Significantly, many of these tertiary and quaternary protein structure scaffolds have been engineered for phage display, allowing rapid selection of potent sequences for desired targets.…”

Section: Fragment-based Designmentioning

confidence: 99%

Systematic Targeting of Protein–Protein Interactions

Modell

Blosser

Arora

2016

Trends in Pharmacological Sciences

155

143

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Over the past decade, protein-protein interactions have gone from being neglected as “undruggable” to being considered attractive targets for the development of therapeutics. Recent advances in computational analysis, fragment-based screening and molecular design have revealed promising strategies to address the basic molecular recognition challenge: how to target large protein surfaces with specificity. Several systematic and complementary workflows have been developed to yield successful inhibitors of protein-protein interactions. Herein we review the major contemporary approaches utilized for the discovery of inhibitors and focus on a structure-based workflow, from the selection of a biological target through design.

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Section: Fragment-based Designmentioning

confidence: 99%

Systematic Targeting of Protein–Protein Interactions

Modell

Blosser

Arora

2016

Trends in Pharmacological Sciences

155

143

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“…Phage display selections were carried out using a well-characterized single-framework synthetic antibody library named Library-F [1,5]. Five rounds of solid-phase panning were conducted against seven recombinant protein targets (full-length extracellular domains of Notch1, Notch2, Notch3, Jagged1, Jagged2, Axl and Mer) as described previously [6].…”

Section: Case Studymentioning

confidence: 99%

WeSeqMiner: A Weka package for building machine-learning models for sequence data

Hogan

et al. 2017

Preprint

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In most cases, the application of machine learning techniques to biological sequence data requires a vector representation of the sequences. Extracting the numerical features from sequence data can be time consuming, especially if the user lacks programming skills. To this end, we propose a Weka package called WeSeqMiner, which provides several useful filters for extracting numerical features from sequence data for use in the Weka machine learning workbench. Motivated with an example, we show that the WeSeqMiner package integrates well with the Weka API, allowing transformations to be incorporated into Weka workflows for predictive model generation. WeSeqMiner can be installed by pointing the Weka package manager to the URL github.com/djhogan/WeSeqMiner/raw/master/WeSeqMiner.zip. The Javadoc for WeSeqMiner classes can be accessed at djhogan.github.io/seqminer.

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“…The generation of synthetic antibodies by phage display technology offers an approach for high-throughput production of functional monoclonal antibodies (Adams and Sidhu 2014). To generate synthetic antibodies, libraries are engineered to express and display antigen-binding fragments (Fabs) on the surfaces of bacteriophage particles, and Fabs that recognize an antigen of interest are selected from the library through multiple rounds of in vitro selection.…”

Section: Introductionmentioning

confidence: 99%

A high-throughput pipeline for the production of synthetic antibodies for analysis of ribonucleoprotein complexes

Hong

Laver

Jeon

et al. 2016

RNA

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Post-transcriptional regulation of mRNAs plays an essential role in the control of gene expression. mRNAs are regulated in ribonucleoprotein (RNP) complexes by RNA-binding proteins (RBPs) along with associated protein and noncoding RNA (ncRNA) cofactors. A global understanding of post-transcriptional control in any cell type requires identification of the components of all of its RNP complexes. We have previously shown that these complexes can be purified by immunoprecipitation using anti-RBP synthetic antibodies produced by phage display. To develop the large number of synthetic antibodies required for a global analysis of RNP complex composition, we have established a pipeline that combines (i) a computationally aided strategy for design of antigens located outside of annotated domains, (ii) high-throughput antigen expression and purification in Escherichia coli, and (iii) high-throughput antibody selection and screening. Using this pipeline, we have produced 279 antibodies against 61 different protein components of Drosophila melanogaster RNPs. Together with those produced in our low-throughput efforts, we have a panel of 311 antibodies for 67 RNP complex proteins. Tests of a subset of our antibodies demonstrated that 89% immunoprecipitate their endogenous target from embryo lysate. This panel of antibodies will serve as a resource for global studies of RNP complexes in Drosophila. Furthermore, our high-throughput pipeline permits efficient production of synthetic antibodies against any large set of proteins.

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Synthetic antibody technologies

Cited by 61 publications

References 55 publications

Systematic Targeting of Protein–Protein Interactions

Systematic Targeting of Protein–Protein Interactions

WeSeqMiner: A Weka package for building machine-learning models for sequence data

A high-throughput pipeline for the production of synthetic antibodies for analysis of ribonucleoprotein complexes

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