Schematic comparison of conventional solid-phase peptide synthesis and the newly developed ligation platform, illustrating a streamlined workflow for producing complex peptides with fewer purification steps.

Overcoming Manufacturing Challenges for Complex Peptides

Peptide therapeutics have become an important class of medicines because of their high target specificity and generally favorable safety profiles. They are widely used to treat diabetes, obesity, cancer and numerous chronic diseases. Among the most prominent examples are long-acting GLP-1 therapeutics, many of which contain more than 30 amino acids together with lipid conjugations and non-natural amino acid modifications. While these structural features enhance therapeutic performance, they also make manufacturing significantly more challenging.

According to Kao, conventional peptide synthesis methods often experience declining reaction efficiency when producing long-chain or heavily modified peptides. Lower yields, increased byproduct formation and more complicated purification procedures not only raise manufacturing costs but also make large-scale production and quality consistency more difficult.

 

 

At the core of the new platform is an integrated solid-phase workflow that combines peptide fragment synthesis and ligation within a single reaction system. By eliminating many of the separation and purification steps required in conventional manufacturing processes, the platform streamlines production while improving both efficiency and product quality.

The technology is compatible with a broad range of structurally demanding peptides—including long-chain, cyclic, amphiphilic and chemically modified molecules. Compared with existing approaches, it delivers higher synthesis efficiency and product purity while reducing unwanted byproducts. Its versatility makes it suitable for both laboratory research and industrial-scale manufacturing.

Beyond improving research efficiency, the platform also offers strong potential for large-scale production. By shortening the timeline from early-stage discovery to preclinical development, it could help accelerate the commercialization of next-generation peptide therapeutics.

“Many peptide drug candidates fail not because of molecular design, but because they are too difficult to manufacture efficiently,” Chen said. “Our goal was to build a platform that makes complex peptides easier to produce at scale and easier to translate into real-world therapeutics.”

Bridging Academic Innovation and Industrial Translation

Chen said that successful biotechnology innovation requires more than promising drug concepts—it also depends on manufacturing technologies capable of translating laboratory discoveries into real-world products. The team’s modular fragment design strategy and solid-phase ligation technology enable researchers and pharmaceutical developers to evaluate peptide drug candidates more efficiently, accelerating preclinical research while reducing manufacturing risks during process development.

Beyond technology development, the researchers have actively strengthened connections between academia and industry. The platform supports the synthesis of specialized peptides, synthetic intermediates, impurity reference standards and customized peptide products, providing technical services for academic laboratories, biotechnology startups, contract development and manufacturing organizations (CDMOs), and pharmaceutical companies developing structurally complex peptides. Receiving the 22nd National Innovation Award recognizes the team’s long-term commitment to advancing peptide synthesis technologies while underscoring NYCU’s strengths in pharmaceutical sciences, process engineering and translational research.

Looking ahead, the researchers plan to validate the platform at larger manufacturing scales while expanding international collaborations and industry partnerships. By serving as a bridge between academic innovation and biopharmaceutical manufacturing, they hope to help bring more next-generation peptide therapeutics from the laboratory to clinical development while strengthening Taiwan’s role in advanced peptide manufacturing and precision medicine.