PEARL-seq: A Photoaffinity Platform for the Analysis of Small Molecule-RNA Interactions.

RNA is emerging as a valuable target for the development of novel therapeutic agents. The rational design of RNA-targeting small molecules, however, has been hampered by the relative lack of methods for the analysis of small molecule-RNA interactions. Here, we present our efforts to develop such a platform using photoaffinity labeling.

An overview of DNA-encoded libraries: A versatile tool for drug discovery.

DNA-encoded libraries (DELs) are collections of small molecules covalently attached to amplifiable DNA tags carrying unique information about the structure of each library member. A combinatorial approach is used to construct the libraries with iterative DNA encoding steps, facilitating tracking of the synthetic history of the attached compounds by DNA sequencing. Various screening protocols have been developed which allow protein target binders to be selected out of pools containing up to billions of different small molecules.

Fidelity by design: Yoctoreactor and binder trap enrichment for small-molecule DNA-encoded libraries and drug discovery.

DNA-encoded small-molecule library (DEL) technology allows vast drug-like small molecule libraries to be efficiently synthesized in a combinatorial fashion and screened in a single tube method for binding, with an assay readout empowered by advances in next generation sequencing technology. This approach has increasingly been applied as a viable technology for the identification of small-molecule modulators to protein targets and as precursors to drugs in the past decade. Several strategies for producing and for screening DELs have been devised by both academic and industrial institutions.

Streamlining hit discovery and optimization with a yoctoliter scale DNA reactor.

Background: The field of DNA-encoded technology offers a cutting edge approach to creating 10(9) - 10(12)-size small molecule libraries for the rapid identification of drug-like hits. The YoctoReactor(®) (yR) is the newest DNA-encoded technology and features an innovative and fundamentally different design.

Objective: This technology evaluation presents the basic principles of the yR drug discovery technology platform and discusses its potential as an alternative to current hit discovery methods where high quality and selective drug-like hits can be delivered together with instant structure activity relationships (SAR).

A yoctoliter-scale DNA reactor for small-molecule evolution.

The center of DNA three-way junctions, constituting a yoctoliter (10(-24) L) volume, is applied as an efficient reactor to create DNA-encoded libraries of chemical products. Amino acids and short peptides are linked to oligonucleotides via cleavable and noncleavable linkers. The oligonucleotide sequences contain two universal assembling domains at the center and a distal codon sequence specific for the attached building block.

Allergen-specific polyclonal antibodies reduce allergic disease in a mouse model of allergic asthma.

Background: Recombinant allergen-specific immunoglobulin G (IgG) antibody therapy can reduce allergic asthma symptoms by inhibiting the immunoglobulin E (IgE)-mediated allergic response. This study investigated the effect of intranasally administered allergen-specific monoclonal (mAb) and polyclonal (pAb) antibody on airway inflammation and hyperresponsiveness (AHR) in a mouse model of human asthma.

Methods: Ovalbumin (OVA)-specific IgG2b antibodies were generated by phage display using spleens from OVA-immunized mice, and screening against OVA and finally expressed in CHO cells.