DNA Encoding of Natural Products.

Area of Science:

• Biochemistry
• Medicinal Chemistry
• Synthetic Biology

Background:

• Natural products (NPs) are crucial in drug discovery due to their evolutionary optimization.
• DNA-encoded libraries (DELs) combine DNA barcoding with combinatorial synthesis for efficient screening.
• Current DEL methods face challenges in annotating complex natural product structures.

Purpose of the Study:

• To develop a method for DNA barcoding complex natural products.
• To create a DNA-encoded natural product library (nDEL).
• To facilitate the use of natural products in drug discovery pipelines.

Main Methods:

• Functionality-independent DNA barcoding of natural products.
• Utilizing enzymatic ligation for DNA attachment.
• Employing "split and pool" combinatorial synthesis strategies.

Main Results:

• Successful generation of a DNA-encoded natural product library (nDEL).
• Demonstrated a practical method for annotating complex NPs with DNA barcodes.
• Established a foundation for DNA-encoded natural product screening.

Conclusions:

• The developed nDEL method offers a simple and practical approach to DNA barcoding complex natural products.
• This technique enhances the utility of natural products in drug discovery.
• nDEL technology expands the scope of DEL applications to diverse chemical spaces.