Complex & Modified Peptides Development

Within our Pharmaceutical Development & Manufacturing framework, Drug Substance Development provides a rigorous, phase-appropriate path for peptide APIs. Under this umbrella, Peptide Therapeutics Development focuses on complex and chemically modified peptides designed for enhanced performance, manufacturability, and quality.

Sequence Engineering & Modification Strategy Design Service

We translate target profiles into practical peptide designs by evaluating cyclization modes (head-to-tail, side-chain–to–side-chain, and hydrocarbon stapling), hetero- and homodimerization strategies, disulfide patterning, and substitution schemes (D-residues, N-methylation, β-/γ-residues). We also assess PEG length/architecture, lipid anchors, and glycan motifs for solubility, proteolysis resistance, and distribution behavior.

Solid-Phase & Hybrid Synthesis Process Development Service

For linear and conformationally constrained sequences, we develop robust SPPS or hybrid SPPS/solution routes using optimized coupling cycles, base selection, and resin/solvent systems for difficult motifs (e.g., Arg-rich, Pro-rich, sterically hindered residues). We implement orthogonal protection schemes to enable on-resin cyclization, selective side-chain ligations, site-specific lipidation/PEGylation, and late-stage modifications. Process development targets high stepwise fidelity, minimized deletion sequences, and impurity convergence, while generating scalable, batch-written instructions and in-process controls appropriate for regulated manufacture.

Oxidative Folding, Cyclization & Macrocyclization Control Service

For disulfide-containing or macrocyclic peptides, we establish folding and closure conditions that drive the desired topology. Tools include redox buffers, thiol-disulfide exchange mediators, pH/denaturant windows, templated folding aids, and chemoselective ligation pairs. We define kinetic vs. thermodynamic control and set acceptance criteria for isomer ratios, employing orthogonal analytics to verify connectivity and macrocycle integrity.

Advanced Analytical & Structural Characterization Service

We build stability-indicating analytical methods that resolve sequence-related impurities, truncations, epimers, and conjugation variants. Typical packages comprise gradient LC-UV, LC-MS/HRMS, intact mass with deconvolution, peptide mapping, chiral/epimer ratio assays, charge/hydrophilicity profiling, and orthogonal confirmation (e.g., NMR for macrocycles/disulfide connectivities when feasible).

PEGylation, Lipidation & Glyco-Modification Development Service

We design site-selective conjugation strategies to install PEG, lipid, or glycan motifs without compromising sequence integrity. Site choice (N-terminus, Lys ε-amine, engineered handle) and linker chemistry are screened for selectivity, stability, and minimal heterogeneity. We define reaction stoichiometry, quench/cleanup, and polishing steps, and we establish attribute controls for the distribution of conjugated species, residual reagents, and linker-related by-products.

Impurity Profiling & Control Strategy Service

Complex peptides generate characteristic impurity families: deletion sequences, racemization/epimerization, oxidation, deprotection adducts, misfolded disulfides, and over-/under-conjugated species. We map impurity origins to specific unit operations, implement preventive levers (e.g., base strength, coupling reagents, orthogonal deprotection timing), and assign clearance points to purification. A phase-appropriate specification strategy is drafted with reporting/identification/qualification thresholds suitable for peptide APIs.

API Polishing, Purification & Desalting Development Service

We tailor preparative RP-HPLC or mixed-mode chromatographic solutions for challenging hydrophobic or highly cationic peptides, optimizing gradients, ion-pairing agents, and load to resolve near-isobaric impurities. Where needed, multi-dimensional purification or crystallization-assisted polishing is developed. Final desalting, counter-ion exchange, and residual solvent control are integrated to yield a stable API form.

Stability, Degradation Pathways & Pre-Formulation Prototype Service

We elucidate degradation pathways (hydrolysis, deamidation, isomerization, oxidation, and isulfide scrambling) under stress conditions and define kinetic fingerprints. Guided by these data, we propose phase-appropriate pre-formulation prototypes for the API—buffer species, pH windows, antioxidant systems, and lyophilization screens—to protect critical attributes during storage and downstream processing, while keeping the scope strictly within drug substance development.