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Working together, chemists and biologists will be able to develop methods that combine genetic and metabolic engineering to introduce a range of unnatural epitopes onto cells without the restrictions imposed by nature’s biosynthetic machinery and metabolic building blocks. Advances in these technologies will also produce new, multifaceted tactics for landscaping cell surfaces. The potential for these techniques is tremendous. As a professional cell surface engineering services provider, Creative Biolabs is capable of providing customer-satisfied cell surface-based metabolic conjugation services to global clients.
Much of enzyme-mediated labeling requires some aspects of time-intensive genetic engineering for tagged substrates. The continued pursuit of imparting orthogonality without the use of genetic manipulation has ignited the field of metabolic engineering. It is now possible to create new cell-surface epitopes via the metabolic incorporation of unnatural precursors into plasma membrane components. Oligosaccharides are particularly amenable to this type of metabolic engineering since the enzymes and transport proteins in certain biosynthetic pathways are tolerant of unnatural substrates. Cells will take up monosaccharide analogs from the extracellular environment and process them into cell-surface glycoconjugates. In contrast, the pathways for protein biosynthesis are more restrictive, and only the most conservatively modified amino acids are accepted.
Metabolic labeling is particularly advantageous in engineering cell surface proteoglycans, as glycostructures in various forms compose a significant portion of the extracellular matrix and the rapid turnover of these structures ensures rapid metabolic incorporation. In this method, azides were installed on the cell surface using the synthetic azido sugar precursor N-azidoacetylmannosamine (Ac4GalNAz). The precursors were incorporated into mucin-type O-linked glycoproteins in Jurkat cells via the N-acetylgalactosamine (GalNAc) salvage pathway. After 3 days of incubation, the glycostructures were orthogonally labeled with biotinylated triarylphosphine via click-based Staudinger ligation to produce stable cell-surface adducts. This strategy was also used to manipulate cell-cell interactions on peripheral blood mononuclear cells (PBMCs) to achieve targeted apoptosis.
In contrast to the typical approach of modifying cell surfaces outside the body before administering them to patients, metabolic engineering offers a technique to tag cells directly within the organism, eliminating the need for external manipulations. This sophisticated method involves selectively marking cancer cells in a living body by administering a dibenzocyclooctyne doxorubicin conjugate tagged with an alkyne to tumor sites. The strategy has demonstrated efficacy against MDAMB-231 triple-negative breast cancer, LS174T colon cancer, and 4T1 metastatic breast cancer in murine models, while observing significantly reduced harm to healthy cells.
Committed to cell surface conjugation research over years, Creative Biolabs has accumulated strong foundations such as advanced facilities, the latest technologies, and a team of professional experts. With reliable foundations and extensive experience accumulated step-by-step during practice, we are confident in providing every customer with satisfying cell surface-based metabolic conjugation services.
As an industry-leading cell surface engineering services provider, Creative Biolabs is your best partner. If you are interested in cell surface-based metabolic conjugation services or other cell surface engineering services, please feel free to contact us for more information.
All services are only provided for research purposes and Not for clinical use.