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'''Translational glycobiology''' or '''applied glycobiology''' is the branch of [[glycobiology]] and glycochemistry that focuses on developing new [[pharmaceuticals]] through [[glycomics]] and [[glycan|glycoengineering]].<ref name="Koch">{{cite journal | url=http://glycob.oxfordjournals.org/content/early/2016/03/29/glycob.cww026.abstract | title=Fulfilling Koch's postulates in glycoscience: HCELL, GPS and translational glycobiology | author=Robert Sackstein | journal= | year=2016}}</ref> Research in the field aims to use therapeutic [[glycoconjugates]] for preventing [[transplant rejection]], treating various [[bone diseases]], and developing [[cancer vaccine|therapeutic cancer vaccines]] and other [[targeted therapies]].<ref name="Nature">{{cite journal | url=http://www.nature.com/icb/journal/v83/n4/full/icb200555a.html | title=Special Feature: Glycobiology Of Xenotransplantation And Cancer Part I | author=Slovin, S. | journal=Nature | year=2005 | volume=Immunology and Cell Biology | issue=83 | pages=418–428 | doi=10.1111/j.1440-1711.2005.01350.x|display-authors=etal}}</ref><ref name="ncbi">{{cite journal | title=Engineered glycoforms of an antineuroblastoma IgG1 with optimized antibody-dependent cellular cytotoxic activity | author=Umaña P. | journal=Nature | volume=17 | issue=2 | pages=176–80 | year=1999 | pmid=10052355|display-authors=etal| doi=10.1038/6179 }}</ref>
'''Translational glycobiology''' or '''applied glycobiology''' is the branch of [[glycobiology]] and glycochemistry that focuses on developing new [[pharmaceuticals]] through [[glycomics]] and [[glycan|glycoengineering]].<ref name="Koch">{{cite journal | url=http://glycob.oxfordjournals.org/content/early/2016/03/29/glycob.cww026.abstract | title=Fulfilling Koch's postulates in glycoscience: HCELL, GPS and translational glycobiology | author=Robert Sackstein | journal= | year=2016}}</ref> Research in the field aims to use therapeutic [[glycoconjugates]] for preventing [[transplant rejection]], treating various [[bone diseases]], and developing [[cancer vaccine|therapeutic cancer vaccines]] and other [[targeted therapies]].<ref name="Nature">{{cite journal | url=http://www.nature.com/icb/journal/v83/n4/full/icb200555a.html | title=Special Feature: Glycobiology Of Xenotransplantation And Cancer Part I | author=Slovin, S. | journal=Nature | year=2005 | volume=Immunology and Cell Biology | issue=83 | pages=418–428 | doi=10.1111/j.1440-1711.2005.01350.x| pmid=16033538 |display-authors=etal}}</ref><ref name="ncbi">{{cite journal | title=Engineered glycoforms of an antineuroblastoma IgG1 with optimized antibody-dependent cellular cytotoxic activity | author=Umaña P. | journal=Nature | volume=17 | issue=2 | pages=176–80 | year=1999 | pmid=10052355|display-authors=etal| doi=10.1038/6179 }}</ref>


==Drug targets==
==Drug targets==
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Since glycoconjugates play an important role in [[Cell–cell interaction|intercellular interactions]], they serve as viable [[drug target]]s. Multiple current therapeutics target these interactions, and there is ongoing research and development to produce additional ones.
Since glycoconjugates play an important role in [[Cell–cell interaction|intercellular interactions]], they serve as viable [[drug target]]s. 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]].<ref name="Glycotherapy">{{cite journal | url=http://www.sciencedirect.com/science/article/pii/S1074552113003463 | title=Glycotherapy: New Advances Inspire a Reemergence of Glycans in Medicine |author1=Hudak, J. |author2=Bertozzi, C. | journal= Chemistry & Biology| year=2014 | volume=21 | issue=1 | pages=16–37 | doi=10.1016/j.chembiol.2013.09.010}}</ref>
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]].<ref name="Glycotherapy">{{cite journal | title=Glycotherapy: New Advances Inspire a Reemergence of Glycans in Medicine |author1=Hudak, J. |author2=Bertozzi, C. | journal= Chemistry & Biology| year=2014 | volume=21 | issue=1 | pages=16–37 | doi=10.1016/j.chembiol.2013.09.010|pmid = 24269151|pmc=4111574 }}</ref>


By modifying [[CD44|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 (hematopoietic)|homing]] those cells to the bone marrow of their host.<ref name="Koch"/> Once mesenchymal stem cells transmigrate through the bone marrow [[endothelium]], they differentiate into [[osteoblasts]] and begin contributing to [[Ossification|bone formation]]. This technique has been proposed as a potential treatment for numerous bone diseases, including [[osteogenesis imperfecta]].<ref name="HCELL">{{cite journal | author = Sackstein, R. | title = Glycosyltransferase-programmed stereosubstitution (GPS) to create HCELL: engineering a roadmap for cell migration | journal = Immunological Reviews | volume = 230 | issue = 1 | pages = 51–74 | date = Jul 2009 | pmid = 19594629 | pmc = 4306344 | doi = 10.1111/j.1600-065X.2009.00792.x| lay-url=http://pegnac.sdsc.edu/bwhharvard/files/robert_sackstein.pdf|lay-source=Glycosyltransferase-Programmed Stereosubstitution (GPS): Directing Cell Migration via Translational Glycobiology}}</ref>
By modifying [[CD44|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 (hematopoietic)|homing]] those cells to the bone marrow of their host.<ref name="Koch"/> Once mesenchymal stem cells transmigrate through the bone marrow [[endothelium]], they differentiate into [[osteoblasts]] and begin contributing to [[Ossification|bone formation]]. This technique has been proposed as a potential treatment for numerous bone diseases, including [[osteogenesis imperfecta]].<ref name="HCELL">{{cite journal | author = Sackstein, R. | title = Glycosyltransferase-programmed stereosubstitution (GPS) to create HCELL: engineering a roadmap for cell migration | journal = Immunological Reviews | volume = 230 | issue = 1 | pages = 51–74 | date = Jul 2009 | pmid = 19594629 | pmc = 4306344 | doi = 10.1111/j.1600-065X.2009.00792.x| lay-url=http://pegnac.sdsc.edu/bwhharvard/files/robert_sackstein.pdf|lay-source=Glycosyltransferase-Programmed Stereosubstitution (GPS): Directing Cell Migration via Translational Glycobiology}}</ref>


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.{{Citation needed|date=June 2016}} Another treatment is [[cancer immunotherapy]], which directs the immune system to attack tumor cells expressing the targeted [[Tumor antigen|altered glycoconjugates]].<ref name="Frontiers">{{cite journal | url=http://journal.frontiersin.org/article/10.3389/fonc.2015.00138/full | title=Biosynthetic machinery involved in aberrant glycosylation: promising targets for developing of drugs against cancer | author=Vasconcelos-dos-Santos, A. |display-authors=etal | journal=Frontiers in Oncology | year=2015| doi=10.3389/fonc.2015.00138 | volume=5}}</ref>
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.{{Citation needed|date=June 2016}} Another treatment is [[cancer immunotherapy]], which directs the immune system to attack tumor cells expressing the targeted [[Tumor antigen|altered glycoconjugates]].<ref name="Frontiers">{{cite journal | title=Biosynthetic machinery involved in aberrant glycosylation: promising targets for developing of drugs against cancer | author=Vasconcelos-dos-Santos, A. |display-authors=etal | journal=Frontiers in Oncology | year=2015| doi=10.3389/fonc.2015.00138 |pmid = 26161361| pmc=4479729 | volume=5| pages=138 }}</ref>


== See also ==
== See also ==

Revision as of 06:22, 11 March 2019

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.[citation needed] Another treatment is cancer immunotherapy, which directs the immune system to attack tumor cells expressing the targeted altered glycoconjugates.[6]

See also

References

  1. ^ a b Robert Sackstein (2016). "Fulfilling Koch's postulates in glycoscience: HCELL, GPS and translational glycobiology". {{cite journal}}: Cite journal requires |journal= (help)
  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. {{cite journal}}: Unknown parameter |lay-source= ignored (help); Unknown parameter |lay-url= ignored (help)
  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.{{cite journal}}: CS1 maint: unflagged free DOI (link)