PEPTIDES & PROTEINS
Z-flow LPPS technologies
Z-Flow: Automating LPPS development
Cambrex has positioned LPPS as a strategic extension of its capabilities( Figure 2). Process development is led by the Snapdragon Chemistry subsidiary, which integrates automation, advanced process control and data-driven experimentation to accelerate development timelines.
In parallel, Cambrex’ s manufacturing site in Charles City, Iowa, is expanding upstream synthesis and downstream purification capabilities for peptides. Additional centres of excellence provide complementary expertise, including peptide crystallisation for non-chromatographic isolation and purity upgrading, as well as advanced analytical method development and GMP quality control tailored to peptide APIs.
A central element of Cambrex’ s LPPS strategy is the Z-Flow automated development platform( pictured). Z-Flow is a multi-vessel liquid- and slurry-handling system capable of precision reagent dosing, controlled mixing, repeated aqueous washing, and phase separation. The platform supports both Fmoc- and Cbz-protected amino-acid chemistries, enabling flexibility in protecting-group selection based on sustainability and sequence compatibility.
In a typical LPPS cycle, the N-terminal protecting group is removed under basic or hydrogenolytic conditions, followed by aqueous washes that remove excess reagents while the tagged peptide remains in the organic phase. Activated amino acids are prepared in separate vessels and transferred for coupling. This cycle is repeated in a programmable fashion to reach the desired fragment length.
For a representative fragment of 10 ~ 15 mer used in medium-size peptides, LPPS synthesis on Z-Flow can be completed in approximately two days, compared with one to two weeks of manual laboratory work. Crude fragment purities exceeding 90 % are routinely achieved, with per-residue yields typically in the 93-95 % range.
Processes developed on Z-Flow are readily scalable to pilot reactors exceeding 100 L, supporting multikilogram production of crude peptide intermediates. At commercial scale, the combined benefits of reduced solvent usage, shorter cycle times and improved scalability translate into cost-of-goods reductions exceeding 50 % relative to traditional SPPS routes.
Outlook
LPPS predates SPPS, but its modern resurgence reflects the changing demands of peptide therapeutics. As structurally complex peptides move into late-stage development and commercial production, manufacturing platforms must deliver scalability, sustainability and supplychain flexibility at unprecedented levels. Fragment-based LPPS, enabled by advances in tag design and automation, offers a credible and increasingly proven solution.
With continued innovation in coupling chemistry, process automation, and regulatory strategy, LPPS is positioned to become a mainstream manufacturing platform for large-volume peptide APIs. Cambrex’ s integrated approach, combining non-proprietary tagassisted LPPS with automated development and global manufacturing infrastructure, illustrates how solution-phase chemistry can be transformed into a modern, industrially robust technology for the next generation of peptide drugs. ●
Dr Eric Fang
SITE HEAD & GENERAL MANAGER,
SNAPDRAGON CHEMISTRY, A CAMBREX COMPANY
k + 1 617-894-1899 J eric. fang @ cambrex. com j www. cambrex. com
32 SPECIALITY CHEMICALS MAGAZINE ESTABLISHED 1981