Translational glycobiology

Translational glycobiology or applied glycobiology is the branch of glycobiology and glycochemistry that focuses on developing new pharmaceuticals through glycomics and glycoengineering.[1] Research in the field aims to use therapeutic glycoconjugates for preventing transplant rejection, treating various bone diseases, and developing therapeutic cancer vaccines and other targeted therapies.[2][3]

Drug targets
The glycosaminoglycan structure of heparin.

Since glycoconjugates play an important role in intercellular interactions, they serve as viable drug targets. Multiple current therapeutics target these interactions, and there is ongoing research and development to produce additional ones.

These interactions can be controlled by encouraging or inhibiting the presence of those glycans that mediate them, which is the mechanism of action for a number of extant drugs, including heparin, erythropoietin, the antivirals oseltamivir and zanamivir, and the Hib vaccine.[4]

By modifying CD44 antigens using glycosyltransferase-programmed stereosubstitution (GPS), the HCELL expression on the surfaces of human mesenchymal stem cells and hematopoietic stem cells can be enforced, effectively homing those cells to the bone marrow of their host.[1] Once mesenchymal stem cells transmigrate through the bone marrow endothelium, they differentiate into osteoblasts and begin contributing to bone formation. This technique has been proposed as a potential treatment for numerous bone diseases, including osteogenesis imperfecta.[5]

The surfaces of cancer cells often exhibit aberrant glycosylation, which serves to mediate cell proliferation, metastasis, and tumor progression. However, because these glycans often differ from those present on healthy cells, they also serve as candidates to act as cancer biomarkers for use in diagnostics and in developing targeted therapies that discriminate between cancerous cells and normal host tissue. One such therapy involves the use of enzyme inhibitors that target those enzymes involved in the biosynthesis of cancer-associated glycans. Another treatment is cancer immunotherapy, which directs the immune system to attack tumor cells expressing the targeted altered glycoconjugates.[6]

See also

References
  1. Robert Sackstein (2016). "Fulfilling Koch's postulates in glycoscience: HCELL, GPS and translational glycobiology". Glycobiology. 26 (6): 560–570. doi:10.1093/glycob/cww026. PMC 4847618. PMID 26933169.
  2. Slovin, S.; et al. (2005). "Special Feature: Glycobiology Of Xenotransplantation And Cancer Part I". Nature. Immunology and Cell Biology (83): 418–428. doi:10.1111/j.1440-1711.2005.01350.x. PMID 16033538.
  3. Umaña P.; et al. (1999). "Engineered glycoforms of an antineuroblastoma IgG1 with optimized antibody-dependent cellular cytotoxic activity". Nature. 17 (2): 176–80. doi:10.1038/6179. PMID 10052355.
  4. Hudak, J.; Bertozzi, C. (2014). "Glycotherapy: New Advances Inspire a Reemergence of Glycans in Medicine". Chemistry & Biology. 21 (1): 16–37. doi:10.1016/j.chembiol.2013.09.010. PMC 4111574. PMID 24269151.
  5. Sackstein, R. (Jul 2009). "Glycosyltransferase-programmed stereosubstitution (GPS) to create HCELL: engineering a roadmap for cell migration". Immunological Reviews. 230 (1): 51–74. doi:10.1111/j.1600-065X.2009.00792.x. PMC 4306344. PMID 19594629. Lay summary (PDF) – Glycosyltransferase-Programmed Stereosubstitution (GPS): Directing Cell Migration via Translational Glycobiology.
  6. Vasconcelos-dos-Santos, A.; et al. (2015). "Biosynthetic machinery involved in aberrant glycosylation: promising targets for developing of drugs against cancer". Frontiers in Oncology. 5: 138. doi:10.3389/fonc.2015.00138. PMC 4479729. PMID 26161361.
This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.