Advanced Conjugation Processes
Personalized Conjugation Kits |
Custom Bioconjugation Service |
CellMosaic’s advanced conjugation processes have been developed and optimized through custom bioconjugation services. More than 500 projects covering a variety of compounds have been completed as of March 2023. Most of the conjugates made for customers were high-quality product containing over 90% single ratio conjugate or pure conjugate (see examples for various conjugates under custom bioconjugation services). The advanced conjugation processes encompass a wide array of technologies:
- Conjugation workflow
- Labeling and conjugation methods
- Bioanalytical methods, biopurification methods, and bioassay methods
- Modification of biopolymers and small molecules
Unlike medicinal chemistry, conjugation is a complicated process that has not been fully developed and integrated into the drug development process. The usual techniques in medicinal chemistry, such as the optimization of reaction conditions, characterization, purification, and analysis, do not apply to bioconjugation. For example, in a conventional chemical reaction the yield is high, the product is simple, and the reaction is reproducible, but in a biopolymer conjugation the yield is often low and products are complex, usually containing various products and isoforms, including polyconjugated products. A particular reaction condition that works for one biopolymer may not work for another similar biopolymer.
At CellMosaic, we have developed conjugation processes that can be applied readily to any biopolymer. The processes were extensively optimized at CellMosaic and validated by custom synthesis. The process can be completed efficiently. The processes encompass a variety of linkers and linking chemistry that allow stable conjugation or releasable conjugates. Purification and analysis methods have also been developed for a variety of molecules. Characterization methods have been developed for antibodies, proteins, peptides, oligos, and enzymes. Essentially, with little change, we can develop a variety of conjugates utilizing this model and the methods and facilities at CellMosaic.
Methods of Labeling and Conjugating Varieties of Molecules
At CellMosaic, we apply several strategies, including site-directed cysteine mutagenesis, structure characterization, and purification techniques, to obtain single-labeled or site-specific labeled conjugates. This has a huge impact on the quality of the conjugate and ultimately improves conjugate performance.
Peptide labeling and conjugation: We prepare peptide conjugates based on a unique conjugation strategy developed at CellMosaic. Other molecules can be conjugated anywhere on the peptide (C-terminus, N-terminus, or middle). Usually, a single and pure conjugate can be obtained. The advantages of our peptide conjugation strategy are:
- Freedom to attach the drug or molecule of interest at any point in the peptide.
- Other functional groups in the peptide, such as OH, NH2, and SH, will not be affected by the conjugation step.
- The conjugation strategy can easily be tweaked to couple different categories of compounds.
- Short timeline for the development of a conjugation strategy.
Antibody conjugation and antibody fragmentation: We are capable of site-specific antibody labeling and conjugation based on the unique conjugation strategy developed at CellMosaic. We also have a process and methods to obtain antibody fragments for conjugation.
Oligo labeling and conjugation: Some of the obstacles in developing oligonucleotide analogs and siRNA-based therapeutics include limited cellular uptake, poor in vivo pharmacokinetic properties, and a lack of specificity for the target tissues/cells. New studies have shown that chemically conjugated oligonucleotide analogs and siRNAs with bioactive molecules, lipids, and polymers can overcome some of these limitations. On the other hand, oligos can be designed that selectively target the gene and are great for carrying small molecule drugs to the disease target.
We prepare oligo-based conjugates using a unique conjugation strategy developed at CellMosaic. Other molecules can be conjugated anywhere on the oligo (3', 5', or via a modified base) in either the solid phase or post-synthesis solution phase. Usually a single and pure conjugate can be obtained. The advantages of our oligo conjugation strategy are:
- Freedom to attach a drug or molecule of interest at any point in the oligo.
- Other functional groups in the molecule, such as OH, NH2, and SH, will not be affected by the conjugation step.
- The conjugation strategy can easily be tweaked to couple different categories of compounds.
- Short timeline for the development of a conjugation strategy.
Protein labeling and conjugation: At CellMosaic, we use a combination of strategies, including mutagenesis, purification, and labeling technologies, to produce high-quality conjugates.