SE5:E2: The Macrocyclic Mullet

What happens when the textbook SAR playbook stops working? On this episode of Pharm to Table, Rob Garbaccio joins Dani and LC to share the discovery story behind enlicitide (MK-0616), a journey filled with unusual SAR, creative problem-solving, and plenty of chemistry twists along the way. From issue-driven drug design to non-canonical amino acids and modular synthesis strategies, this conversation offers a behind-the-scenes look at how real medicines are discovered. If you're training as a chemist today, this is a story you won't want to miss.

If you enjoyed this chapter of the enlicitide story, stay tuned—we've got plenty more peptide chemistry, process development adventures, and behind-the-scenes drug discovery stories coming your way this season.

Read some of the papers we discussed today:

Discovery Process of Enlicitide, a Highly Engineered Macrocyclic Peptide Therapeutic, through Issue-Driven Fragment-Based Synthetic Assembly and SAR - ⁠J. Med. Chem.⁠

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