
Mendelspod Podcast Beyond GLP-1: Why Peptides Are Back at the Center of Drug Discovery with Charlie Johannes and Tomi Sawyer
Apr 7, 2026
Charlie Johannes, medicinal chemist and peptide drug leader, and Tomi Sawyer, veteran peptide entrepreneur, explore why peptides are resurging beyond GLP-1 hype. They discuss new chemistry and noncanonical amino acids, screening platforms that find hard binders, advances in oral delivery and permeability, AI’s promise and limits with novel chemistries, and the human challenge of turning data into real innovation.
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GLP-1 Catalyzed The Peptide Renaissance
- GLP-1 drugs reignited interest in peptides by proving long peptides can be modified for long half-life and massive market demand.
- Lipid attachments and N-terminal changes (e.g., semaglutide, liraglutide) enabled once-daily or weekly dosing and spurred broad investment.
Non‑Canonical Chemistry Unlocks Peptide Properties
- Expanding chemical space with non‑canonical amino acids lets medicinal chemists encode PK and binding features directly into peptides.
- Modifications like N‑methylation and D‑amino acids mask backbone polarity and improve permeability and half‑life.
Peptides Fill The Small Molecule‑Biologic Gap
- Peptides occupy a middle ground between small molecules and biologics, offering tunable size and delivery modes.
- They can be made orally available via passive permeability (like cyclosporine) or with permeation enhancers such as SNAC or caprate.
