Micelle-Promoted Reductive Amination of DNA-Conjugated Amines for DNA-Encoded Library Synthesis

Area of Science:

• Medicinal Chemistry
• Organic Synthesis
• Biotechnology

Background:

• DNA-encoded libraries (DELs) are crucial for hit identification in drug discovery, requiring efficient chemical transformations.
• Reductive amination is a key reaction for synthesizing C-N bonds in pharmaceuticals, but on-DNA methods are limited.

Purpose of the Study:

• To develop a highly efficient and broadly applicable on-DNA reductive amination procedure for DNA-encoded library synthesis.
• To demonstrate the utility of TPGS-750-M surfactant in facilitating this reaction on DNA-conjugated substrates.

Main Methods:

• Application of TPGS-750-M surfactant to on-DNA reductive amination of DNA-conjugated amines with various aldehydes.
• Compatibility testing with DNA amplification and sequencing protocols.

Main Results:

• Achieved highly efficient conversions in on-DNA reductive amination reactions.
• Demonstrated broad substrate scope, including heterocyclic and aliphatic aldehydes relevant to drug discovery.
• Confirmed compatibility with essential downstream DNA analysis techniques.

Conclusions:

• The developed TPGS-750-M mediated on-DNA reductive amination is a robust method for DEL synthesis.
• This procedure enhances the diversity and efficiency of generating potential drug candidates via DEL technology.