Selections and Screenings of DNA-Encoded Chemical Libraries against Enzyme and Cellular Targets.

  title={Selections and Screenings of DNA-Encoded Chemical Libraries against Enzyme and Cellular Targets.},
  author={Alexander Lee Satz and Letian Kuai and Xuanjia Peng},
  journal={Bioorganic \& medicinal chemistry letters},

Evolution of the Selection Methods of DNA-Encoded Chemical Libraries.

The laboratory has been using DNA-programmed affinity labeling (DPAL) as the main strategy to develop new DEL selection methods, which have significantly widened the target scope of DELs and enabled the functional and potentially phenotypic assays ofdels beyond simple binding.

Strategies for developing DNA-encoded libraries beyond binding assays

The recent progress in using DNA-encoded chemical libraries to interrogate complex biological targets and their potential to identify structures that elicit function or possess other useful properties are discussed.

Recent Advances on the Selection Methods of DNA‐Encoded Libraries

The “classic” DEL selection methods with purified proteins on solid phase are covered, and then the strategies to realize DEL selections in solution phase are discussed, and the emerging approaches for DELs to interrogate complex biological targets are focused on.

Converting Double-Stranded DNA-Encoded Libraries (DELs) to Single-Stranded Libraries for More Versatile Selections

It is shown that dsD ELs could be efficiently converted to ssDELs and used for affinity-based selections either with purified proteins or on live cells.

Maximizing the integration of virtual and experimental screening in hit discovery

The case studies discussed here demonstrate the benefits of complementary strategies such as focused and iterative screening, together with the use of artificial intelligence methods, for their efficient integration.



Beyond protein binding: recent advances in screening DNA-encoded libraries.

A format that demands hits exhibit high selectivity for target vs. off-targets, a protocol to screen for enzyme inhibitors and another to identify organocatalysts in a DEL are reviewed.

Off-DNA DNA-Encoded Library Affinity Screening.

A solid-phase DEL and droplet-based microfluidic screening is used to separate the DEL member from its DNA tag, for subsequent in-droplet laser-induced fluorescence polarization (FP) detection of target binding, obviating DNA tag interference.

Activity-Based DNA-Encoded Library Screening.

This miniaturized screening platform paves the way toward applying DELs to more complex targets (signaling pathways, cellular response) and represents a distributable approach to small molecule discovery.

Cell-Based Selection Expands the Utility of DNA-Encoded Small-Molecule Library Technology to Cell Surface Drug Targets: Identification of Novel Antagonists of the NK3 Tachykinin Receptor.

This work uses a cell-based method for identifying small-molecule ligands from DNA-encoded libraries against integral membrane protein targets to identify novel, potent, and specific inhibitors of NK3, a member of the tachykinin family of G-protein coupled receptors (GPCRs).

Selection of DNA-encoded Libraries to Protein Targets Within and On Living Cells.

The selection of DNA-encoded small molecule libraries against protein targets within the cytosol and on the surface of live cells provides a strategy for selection of DELs against challenging targets that cannot be expressed and purified as active.

What Do You Get from DNA-Encoded Libraries?

  • A. Satz
  • Biology
    ACS medicinal chemistry letters
  • 2018
What to expect when you run a DEL screen is discussed and guidelines for library design are contemplated, and some visionary work is considered and extrapolate to the future.

Selection of DNA-encoded chemical libraries against endogenous membrane proteins on live cells

A method to label membrane proteins with a DNA tag has been developed that enables the selection of DNA-encoded chemical libraries against endogenous membrane proteins on live cells without overexpression or any other genetic manipulation.

Small-Molecule Positive Allosteric Modulators of the β2-Adrenoceptor Isolated from DNA-Encoded Libraries

The first β2AR small-molecule positive allosteric modulators (PAMs) are discovered and characterized using the recently developed approach for screening G protein–coupled receptors (GPCRs) with DNA-encoded small- molecule libraries, and introduced.