3-fluoroazetidinecarboxylic acids and trans,trans-3,4-difluoroproline as peptide scaffolds: inhibition of pancreatic cancer cell growth by a fluoroazetidine iminosugar
Reverse aldol opening renders amides of 3-hydroxyazetidinecarboxylic acids (3-OH-Aze) unstable above pH 8. Aze, found in sugar beet, is mis-incorporated for proline in peptides in humans and is associated with multiple sclerosis and teratogenesis. Aze-containing peptides may be oxygenated by prolyl...
| Main Authors: | , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
American Chemical Society
2015
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| _version_ | 1797090924351717376 |
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| author | Liu, Z Jenkinson, S Vermaas, T Adachi, I Wormald, M Hata, Y Kurashima, Y Kaji, A Yu, C Kato, A Fleet, G |
| author_facet | Liu, Z Jenkinson, S Vermaas, T Adachi, I Wormald, M Hata, Y Kurashima, Y Kaji, A Yu, C Kato, A Fleet, G |
| author_sort | Liu, Z |
| collection | OXFORD |
| description | Reverse aldol opening renders amides of 3-hydroxyazetidinecarboxylic acids (3-OH-Aze) unstable above pH 8. Aze, found in sugar beet, is mis-incorporated for proline in peptides in humans and is associated with multiple sclerosis and teratogenesis. Aze-containing peptides may be oxygenated by prolyl hydroxylases resulting in potential damage of the protein by a reverse aldol of the hydroxyazetidine; this, rather than changes in conformation, may account for the deleterious effects of Aze. This paper describes the synthesis of 3-fluoro-Aze amino acids as hydroxy-Aze analogues which are not susceptible to aldol cleavage. 4-(Azidomethyl)-3-fluoro-Aze and 3,4-difluoroproline are new peptide building blocks. trans,trans-2,4-Dihydroxy-3-fluoroazetidine, an iminosugar, inhibits the growth of pancreatic cancer cells to a similar degree as gemcitabine. |
| first_indexed | 2024-03-07T03:25:38Z |
| format | Journal article |
| id | oxford-uuid:b8edafc6-a1f8-4813-a5af-c59ecdcf24af |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T03:25:38Z |
| publishDate | 2015 |
| publisher | American Chemical Society |
| record_format | dspace |
| spelling | oxford-uuid:b8edafc6-a1f8-4813-a5af-c59ecdcf24af2022-03-27T04:59:35Z3-fluoroazetidinecarboxylic acids and trans,trans-3,4-difluoroproline as peptide scaffolds: inhibition of pancreatic cancer cell growth by a fluoroazetidine iminosugarJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:b8edafc6-a1f8-4813-a5af-c59ecdcf24afEnglishSymplectic Elements at OxfordAmerican Chemical Society2015Liu, ZJenkinson, SVermaas, TAdachi, IWormald, MHata, YKurashima, YKaji, AYu, CKato, AFleet, GReverse aldol opening renders amides of 3-hydroxyazetidinecarboxylic acids (3-OH-Aze) unstable above pH 8. Aze, found in sugar beet, is mis-incorporated for proline in peptides in humans and is associated with multiple sclerosis and teratogenesis. Aze-containing peptides may be oxygenated by prolyl hydroxylases resulting in potential damage of the protein by a reverse aldol of the hydroxyazetidine; this, rather than changes in conformation, may account for the deleterious effects of Aze. This paper describes the synthesis of 3-fluoro-Aze amino acids as hydroxy-Aze analogues which are not susceptible to aldol cleavage. 4-(Azidomethyl)-3-fluoro-Aze and 3,4-difluoroproline are new peptide building blocks. trans,trans-2,4-Dihydroxy-3-fluoroazetidine, an iminosugar, inhibits the growth of pancreatic cancer cells to a similar degree as gemcitabine. |
| spellingShingle | Liu, Z Jenkinson, S Vermaas, T Adachi, I Wormald, M Hata, Y Kurashima, Y Kaji, A Yu, C Kato, A Fleet, G 3-fluoroazetidinecarboxylic acids and trans,trans-3,4-difluoroproline as peptide scaffolds: inhibition of pancreatic cancer cell growth by a fluoroazetidine iminosugar |
| title | 3-fluoroazetidinecarboxylic acids and trans,trans-3,4-difluoroproline as peptide scaffolds: inhibition of pancreatic cancer cell growth by a fluoroazetidine iminosugar |
| title_full | 3-fluoroazetidinecarboxylic acids and trans,trans-3,4-difluoroproline as peptide scaffolds: inhibition of pancreatic cancer cell growth by a fluoroazetidine iminosugar |
| title_fullStr | 3-fluoroazetidinecarboxylic acids and trans,trans-3,4-difluoroproline as peptide scaffolds: inhibition of pancreatic cancer cell growth by a fluoroazetidine iminosugar |
| title_full_unstemmed | 3-fluoroazetidinecarboxylic acids and trans,trans-3,4-difluoroproline as peptide scaffolds: inhibition of pancreatic cancer cell growth by a fluoroazetidine iminosugar |
| title_short | 3-fluoroazetidinecarboxylic acids and trans,trans-3,4-difluoroproline as peptide scaffolds: inhibition of pancreatic cancer cell growth by a fluoroazetidine iminosugar |
| title_sort | 3 fluoroazetidinecarboxylic acids and trans trans 3 4 difluoroproline as peptide scaffolds inhibition of pancreatic cancer cell growth by a fluoroazetidine iminosugar |
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