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Synthesis development towards new pyranoside-based β4GalT7 inhibitors

Bengtsson, Dennis LU (2015) KOK820 20151
Centre for Analysis and Synthesis
Abstract
Proteoglycans (PG) are comprised of a core protein with a varying number of glycosaminoglycan (GAG) chains attached. Both PGs and GAG chains are involved in biological processes such as cell growth and dif-ferentiation. Both their structure and the expression of enzymes involved in their biosynthesis differ between cancer cells and healthy cells. Heparan sulfate(HS) and chondroitin sulfate/dermatan sulfate (CS/DS) GAG chains are primarily involved in cellular signaling. The second step in HS and CS/DS GAG chain synthesis is galactosylation of the unusual carbohydrate xylose, catalyzed by the enzyme β-1,4-Galactosyltransferase 7 (β4GalT7). β-D-xylopyranosides with hydrophobic aglycons, modified at one hydroxyl group has previous-ly been... (More)
Proteoglycans (PG) are comprised of a core protein with a varying number of glycosaminoglycan (GAG) chains attached. Both PGs and GAG chains are involved in biological processes such as cell growth and dif-ferentiation. Both their structure and the expression of enzymes involved in their biosynthesis differ between cancer cells and healthy cells. Heparan sulfate(HS) and chondroitin sulfate/dermatan sulfate (CS/DS) GAG chains are primarily involved in cellular signaling. The second step in HS and CS/DS GAG chain synthesis is galactosylation of the unusual carbohydrate xylose, catalyzed by the enzyme β-1,4-Galactosyltransferase 7 (β4GalT7). β-D-xylopyranosides with hydrophobic aglycons, modified at one hydroxyl group has previous-ly been shown to have both initiating and inhibitory effects on β4GalT7 catalyzed HS and CS/DS GAG chain biosynthesis. To gain more knowledge about both the biological and the pathobiological role of HS and CS/DS GAG chains, as well as to generate potential lead compunds for future drugs targeting diseases de-pendent on GAG chains, the development of new, more efficient β4GalT7 inhibitors is vital. Synthetic routes for three new β-D-xylopyranoside-based potential β4GalT7 inhibitors have been developed. The xylose moiety of each potential inhibitor has been modified at both the C-2, and the C-4 hydroxyl group, to produce epi-, methoxy-, and deoxy-analogs. When a synthetic protocol for a complete series of 2,4-modified fluoro-, epi-, methoxy-, and deoxy-2-naphtyl β-D-xylopyranosides has been developed, their inhibitory effects on β4GalT7 will be investigated. (Less)
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author
Bengtsson, Dennis LU
supervisor
organization
course
KOK820 20151
year
type
H2 - Master's Degree (Two Years)
subject
keywords
organisk kemi, organic chemistry
language
English
id
7520418
date added to LUP
2015-10-15 16:31:31
date last changed
2015-10-15 16:31:31
@misc{7520418,
  abstract     = {Proteoglycans (PG) are comprised of a core protein with a varying number of glycosaminoglycan (GAG) chains attached. Both PGs and GAG chains are involved in biological processes such as cell growth and dif-ferentiation. Both their structure and the expression of enzymes involved in their biosynthesis differ between cancer cells and healthy cells. Heparan sulfate(HS) and chondroitin sulfate/dermatan sulfate (CS/DS) GAG chains are primarily involved in cellular signaling. The second step in HS and CS/DS GAG chain synthesis is galactosylation of the unusual carbohydrate xylose, catalyzed by the enzyme β-1,4-Galactosyltransferase 7 (β4GalT7). β-D-xylopyranosides with hydrophobic aglycons, modified at one hydroxyl group has previous-ly been shown to have both initiating and inhibitory effects on β4GalT7 catalyzed HS and CS/DS GAG chain biosynthesis. To gain more knowledge about both the biological and the pathobiological role of HS and CS/DS GAG chains, as well as to generate potential lead compunds for future drugs targeting diseases de-pendent on GAG chains, the development of new, more efficient β4GalT7 inhibitors is vital. Synthetic routes for three new β-D-xylopyranoside-based potential β4GalT7 inhibitors have been developed. The xylose moiety of each potential inhibitor has been modified at both the C-2, and the C-4 hydroxyl group, to produce epi-, methoxy-, and deoxy-analogs. When a synthetic protocol for a complete series of 2,4-modified fluoro-, epi-, methoxy-, and deoxy-2-naphtyl β-D-xylopyranosides has been developed, their inhibitory effects on β4GalT7 will be investigated.},
  author       = {Bengtsson, Dennis},
  keyword      = {organisk kemi,organic chemistry},
  language     = {eng},
  note         = {Student Paper},
  title        = {Synthesis development towards new pyranoside-based β4GalT7 inhibitors},
  year         = {2015},
}