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DNA Conjugates as Tool Compounds for DEL Selections.

David I Israel1

  • 1HitGen Inc., Chengdu, Sichuan, China. david.israel@hitgen.com.

Methods in Molecular Biology (Clifton, N.J.)
|September 9, 2022
PubMed
Summary
This summary is machine-generated.

DNA-conjugated small molecules aid in discovering novel compounds that bind target proteins. These tool compounds validate targets, optimize selection methods, and serve as positive controls in DNA-encoded library (DEL) selections.

Keywords:
Binding assayDEL selectionsDNA conjugatePositive controlTool compoundqPCR

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Area of Science:

  • Chemical biology
  • Drug discovery
  • Molecular biology

Background:

  • DNA-encoded library (DEL) selections identify novel small molecules binding to target proteins.
  • Validated ligands are crucial for optimizing DEL selection methods and validating targets.
  • Tool compounds are needed to serve as positive controls in DEL experiments.

Purpose of the Study:

  • To discuss the design, synthesis, and application of DNA conjugate tool compounds for DEL selections.
  • To provide an example of a DNA conjugate targeting the CCR5 receptor.
  • To demonstrate the utility of these conjugates in optimizing selection conditions and as positive controls.

Main Methods:

  • Design and synthesis of DNA conjugates using known small molecule or peptide ligands.
  • Utilizing DNA conjugates in preselection binding assays to validate target proteins.
  • Employing DNA conjugates as spike-in positive controls in DEL selection experiments.

Main Results:

  • Demonstrated the successful design and synthesis of a DNA conjugate for the CCR5 receptor.
  • Showcased the use of this conjugate to optimize DEL selection conditions.
  • Validated the conjugate's effectiveness as a spike-in positive control in a DEL selection.

Conclusions:

  • DNA-conjugated tool compounds are valuable for validating targets and optimizing DEL selection processes.
  • These methods are versatile, applicable to both soluble and cell-surface protein targets.
  • The described approach supports the discovery of novel binders across various compound types.