Effect of five-membered sugar mimics on mammalian glycogen-degrading enzymes and various glucosidases.
We investigated inhibitory activities of five-membered sugar mimics toward glycogen-degrading enzymes and a variety of glucosidases. 1,4-Dideoxy-1,4-imino-D-arabinitol (D-AB1) is known to be a potent inhibitor of glycogen phosphorylase. However, the structural modification of D-AB1, such as its enan...
| Päätekijät: | , , , , , , , , , |
|---|---|
| Aineistotyyppi: | Journal article |
| Kieli: | English |
| Julkaistu: |
2008
|
| _version_ | 1826280532029210624 |
|---|---|
| author | Minami, Y Kuriyama, C Ikeda, K Kato, A Takebayashi, K Adachi, I Fleet, G Kettawan, A Okamoto, T Asano, N |
| author_facet | Minami, Y Kuriyama, C Ikeda, K Kato, A Takebayashi, K Adachi, I Fleet, G Kettawan, A Okamoto, T Asano, N |
| author_sort | Minami, Y |
| collection | OXFORD |
| description | We investigated inhibitory activities of five-membered sugar mimics toward glycogen-degrading enzymes and a variety of glucosidases. 1,4-Dideoxy-1,4-imino-D-arabinitol (D-AB1) is known to be a potent inhibitor of glycogen phosphorylase. However, the structural modification of D-AB1, such as its enantiomerization, epimerization at C-2 and/or C-3, introduction of a substituent to C-1, and replacement of the ring nitrogen by sulfur, markedly lowered or abolished its inhibition toward the enzyme. The present work elucidated that d-AB1 was also a good inhibitor of the de-branching enzyme of glycogen, amylo-1,6-glucosidase, with a IC(50) value of 8.4 microM. In the present work, the de-sulfonated derivative of salacinol was isolated from the roots of Salacia oblonga and found to be a potent inhibitor of rat intestinal isomaltase with an IC(50) value of 0.64 microM. On the other hand, salacinol showed a much more potent inhibitory activity toward maltase in Caco-2 cell model system than its de-sulfonated derivative, with an IC(50) value of 0.5 microM, and was further a stronger inhibitor of human lysosomal alpha-glucosidase than the derivative (IC(50)=0.34 microM). This indicates that the sulfate in the side chain plays an important role in the specificity of enzyme inhibition. |
| first_indexed | 2024-03-07T00:15:06Z |
| format | Journal article |
| id | oxford-uuid:7a8f6043-420c-4e73-ad8c-a30cc9fe782c |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T00:15:06Z |
| publishDate | 2008 |
| record_format | dspace |
| spelling | oxford-uuid:7a8f6043-420c-4e73-ad8c-a30cc9fe782c2022-03-26T20:44:56ZEffect of five-membered sugar mimics on mammalian glycogen-degrading enzymes and various glucosidases.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:7a8f6043-420c-4e73-ad8c-a30cc9fe782cEnglishSymplectic Elements at Oxford2008Minami, YKuriyama, CIkeda, KKato, ATakebayashi, KAdachi, IFleet, GKettawan, AOkamoto, TAsano, NWe investigated inhibitory activities of five-membered sugar mimics toward glycogen-degrading enzymes and a variety of glucosidases. 1,4-Dideoxy-1,4-imino-D-arabinitol (D-AB1) is known to be a potent inhibitor of glycogen phosphorylase. However, the structural modification of D-AB1, such as its enantiomerization, epimerization at C-2 and/or C-3, introduction of a substituent to C-1, and replacement of the ring nitrogen by sulfur, markedly lowered or abolished its inhibition toward the enzyme. The present work elucidated that d-AB1 was also a good inhibitor of the de-branching enzyme of glycogen, amylo-1,6-glucosidase, with a IC(50) value of 8.4 microM. In the present work, the de-sulfonated derivative of salacinol was isolated from the roots of Salacia oblonga and found to be a potent inhibitor of rat intestinal isomaltase with an IC(50) value of 0.64 microM. On the other hand, salacinol showed a much more potent inhibitory activity toward maltase in Caco-2 cell model system than its de-sulfonated derivative, with an IC(50) value of 0.5 microM, and was further a stronger inhibitor of human lysosomal alpha-glucosidase than the derivative (IC(50)=0.34 microM). This indicates that the sulfate in the side chain plays an important role in the specificity of enzyme inhibition. |
| spellingShingle | Minami, Y Kuriyama, C Ikeda, K Kato, A Takebayashi, K Adachi, I Fleet, G Kettawan, A Okamoto, T Asano, N Effect of five-membered sugar mimics on mammalian glycogen-degrading enzymes and various glucosidases. |
| title | Effect of five-membered sugar mimics on mammalian glycogen-degrading enzymes and various glucosidases. |
| title_full | Effect of five-membered sugar mimics on mammalian glycogen-degrading enzymes and various glucosidases. |
| title_fullStr | Effect of five-membered sugar mimics on mammalian glycogen-degrading enzymes and various glucosidases. |
| title_full_unstemmed | Effect of five-membered sugar mimics on mammalian glycogen-degrading enzymes and various glucosidases. |
| title_short | Effect of five-membered sugar mimics on mammalian glycogen-degrading enzymes and various glucosidases. |
| title_sort | effect of five membered sugar mimics on mammalian glycogen degrading enzymes and various glucosidases |
| work_keys_str_mv | AT minamiy effectoffivememberedsugarmimicsonmammalianglycogendegradingenzymesandvariousglucosidases AT kuriyamac effectoffivememberedsugarmimicsonmammalianglycogendegradingenzymesandvariousglucosidases AT ikedak effectoffivememberedsugarmimicsonmammalianglycogendegradingenzymesandvariousglucosidases AT katoa effectoffivememberedsugarmimicsonmammalianglycogendegradingenzymesandvariousglucosidases AT takebayashik effectoffivememberedsugarmimicsonmammalianglycogendegradingenzymesandvariousglucosidases AT adachii effectoffivememberedsugarmimicsonmammalianglycogendegradingenzymesandvariousglucosidases AT fleetg effectoffivememberedsugarmimicsonmammalianglycogendegradingenzymesandvariousglucosidases AT kettawana effectoffivememberedsugarmimicsonmammalianglycogendegradingenzymesandvariousglucosidases AT okamotot effectoffivememberedsugarmimicsonmammalianglycogendegradingenzymesandvariousglucosidases AT asanon effectoffivememberedsugarmimicsonmammalianglycogendegradingenzymesandvariousglucosidases |