Synthesis development towards new pyranoside-based β4GalT7 inhibitors
(2015) KOK820 20151Centre 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)
Please use this url to cite or link to this publication:
http://lup.lub.lu.se/student-papers/record/7520418
- author
- Bengtsson, Dennis LU
- supervisor
- organization
- course
- KOK820 20151
- year
- 2015
- 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}}, language = {{eng}}, note = {{Student Paper}}, title = {{Synthesis development towards new pyranoside-based β4GalT7 inhibitors}}, year = {{2015}}, }