One-bead-one-compound library of end-capped dipeptides and deconvolution by microflow NMR

Area of Science:

• Medicinal Chemistry
• Chemical Biology
• Drug Discovery

Background:

• Developing novel small molecules with biological activity is crucial for advancing therapeutic research.
• Traditional methods for library synthesis and decoding can be complex and time-consuming.

Purpose of the Study:

• To design and synthesize a diverse library of end-capped dipeptides for biological screening.
• To develop an efficient method for decoding one-bead-one-compound libraries.

Main Methods:

• A library of approximately 1500 end-capped dipeptides was synthesized manually on polystyrene beads using the mix-and-split method.
• Compounds were cleaved into 384-well plates for high-throughput screening.
• Individual compounds were decoded using mass spectrometry and microflow NMR spectroscopy.

Main Results:

• A diverse library of end-capped dipeptides was successfully synthesized and prepared for screening.
• A novel decoding strategy combining mass spectrometry and microflow NMR spectroscopy was implemented.
• This approach simplifies the deconvolution of one-bead-one-compound libraries, eliminating the need for complex encoding strategies.

Conclusions:

• The developed method provides an efficient way to synthesize and decode diverse chemical libraries.
• This approach facilitates the identification of novel small molecules with potential biological activity.
• The simplified decoding strategy enhances the utility of bead-based combinatorial chemistry for drug discovery.