We are currently witnessing a Golden Age of peptides. As of 2024, the PepTherDia database reports 121 peptides on the market. Between 2016 and 2024, the U.S. FDA approved 33 peptide-based drugs, accounting for 8% of all drug approvals during this period. These modern peptides often exhibit significant structural innovation, including (bi)cyclic architectures, larger molecular size, the incorporation of non-proteinogenic amino acids, and chemical modifications such as PEGylation or fatty acid conjugation. Moreover, industrial-scale production — often requiring multi-kilogram quantities — presents considerable manufacturing challenges.
This progress has been made possible thanks to the foundational work of R. Bruce Merrifield, whose development of Solid-Phase Peptide Synthesis (SPPS) in the 1960s revolutionized the field. SPPS remains essential for both small-scale research and large-scale pharmaceutical production. While the core principle of SPPS has endured, synthetic strategies have continually evolved. Notably, Liquid-Phase Peptide Synthesis (LPPS) is emerging as a viable industrial alternative. LPPS follows the SPPS philosophy but operates in solution using soluble supports (TAGs) rather than solid resins.
This presentation will highlight our lab’s contributions to advancing both SPPS and LPPS methodologies, focusing on innovations in resins, linkers, protecting groups, and coupling agents. These efforts are situated within a broader commitment to sustainability and green peptide synthesis.