{"title":"尿苷5′-单磷酸葡萄糖作为udp -葡萄糖焦磷酸化酶抑制剂的合成","authors":"Ken-Ichi Fujita, Teruhiko Tanigawa, Kiyotaka Machida, Toshio Tanaka, Makoto Taniguchi","doi":"10.1016/S0922-338X(98)80052-4","DOIUrl":null,"url":null,"abstract":"<div><p>Uridine 5′-monophosphate α-<span>d</span>-glucose (UMPG) was evaluated as a novel and potent inhibitor of the enzymatic reaction involved in sugar nucleotide metabolism. UMPG was synthesized by chemical coupling of 2,3,4,6-tetra-<em>O</em>-acetyl-α-<span>d</span>-glucopyranosyl bromide with uridine 5′-monophosphate (UMP) to give uridine 5′-monophosphate 2″,3″,4″,6″-tetra-<em>O</em>-acetyl-α-<span>d</span>-glucose (UMPTAG), followed by deacetylation of UMPTAG with sodium methoxide. In addition to UMPG, UMPTAG showed potent inhibitory activity toward yeast UDPG pyrophosphorylase (UDPG synthetase). UMPG and UMPTAG were competitive with UDPG in the pyrophosphorolytic reaction, with inhibition constants (<em>K</em><sub>i</sub>) of 4.8 and 20.7 μM, respectively, but non-competitive with inorganic pyrophosphate. UMPG and UMPTAG also inhibited the enzyme non-competitively in the reverse reaction to synthesize UDPG from UTP and glucose 1-phosphate (G1P). The acetyl group of UMPTAG was thought to enhance its hydrophobic interaction, possibly with an active site region of the enzyme functional for binding with UDPG.</p></div>","PeriodicalId":15696,"journal":{"name":"Journal of Fermentation and Bioengineering","volume":"86 2","pages":"Pages 145-148"},"PeriodicalIF":0.0000,"publicationDate":"1998-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0922-338X(98)80052-4","citationCount":"3","resultStr":"{\"title\":\"Synthesis of uridine 5′-monophosphate glucose as an inhibitor of UDP-glucose pyrophosphorylase\",\"authors\":\"Ken-Ichi Fujita, Teruhiko Tanigawa, Kiyotaka Machida, Toshio Tanaka, Makoto Taniguchi\",\"doi\":\"10.1016/S0922-338X(98)80052-4\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Uridine 5′-monophosphate α-<span>d</span>-glucose (UMPG) was evaluated as a novel and potent inhibitor of the enzymatic reaction involved in sugar nucleotide metabolism. UMPG was synthesized by chemical coupling of 2,3,4,6-tetra-<em>O</em>-acetyl-α-<span>d</span>-glucopyranosyl bromide with uridine 5′-monophosphate (UMP) to give uridine 5′-monophosphate 2″,3″,4″,6″-tetra-<em>O</em>-acetyl-α-<span>d</span>-glucose (UMPTAG), followed by deacetylation of UMPTAG with sodium methoxide. In addition to UMPG, UMPTAG showed potent inhibitory activity toward yeast UDPG pyrophosphorylase (UDPG synthetase). UMPG and UMPTAG were competitive with UDPG in the pyrophosphorolytic reaction, with inhibition constants (<em>K</em><sub>i</sub>) of 4.8 and 20.7 μM, respectively, but non-competitive with inorganic pyrophosphate. UMPG and UMPTAG also inhibited the enzyme non-competitively in the reverse reaction to synthesize UDPG from UTP and glucose 1-phosphate (G1P). The acetyl group of UMPTAG was thought to enhance its hydrophobic interaction, possibly with an active site region of the enzyme functional for binding with UDPG.</p></div>\",\"PeriodicalId\":15696,\"journal\":{\"name\":\"Journal of Fermentation and Bioengineering\",\"volume\":\"86 2\",\"pages\":\"Pages 145-148\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"1998-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.1016/S0922-338X(98)80052-4\",\"citationCount\":\"3\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Fermentation and Bioengineering\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0922338X98800524\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Fermentation and Bioengineering","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0922338X98800524","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 3
摘要
Uridine 5 ' - monophospate α-d-glucose (UMPG)是一种新型且有效的酶促反应抑制剂,可抑制糖核苷酸代谢。将2,3,4,6-四- o -乙酰基-α-d-葡萄糖吡喃基溴化剂与尿苷5 ' -单磷酸(UMP)化学偶联,得到尿苷5 ' -单磷酸2″,3″,4″,6″-四- o -乙酰基-α-d-葡萄糖(UMPTAG),然后用甲氧基钠将UMPTAG脱乙酰化,合成UMPG。除UMPG外,UMPTAG对酵母UDPG焦磷酸化酶(UDPG合成酶)也有较强的抑制活性。UMPG和UMPTAG对UDPG的抑制常数(Ki)分别为4.8 μM和20.7 μM,与无机焦磷酸盐无竞争关系。UMPG和UMPTAG在UTP和葡萄糖1-磷酸(G1P)合成UDPG的逆反应中也具有非竞争性抑制作用。UMPTAG的乙酰基被认为增强了其疏水相互作用,可能与酶的活性位点区域结合UDPG。
Synthesis of uridine 5′-monophosphate glucose as an inhibitor of UDP-glucose pyrophosphorylase
Uridine 5′-monophosphate α-d-glucose (UMPG) was evaluated as a novel and potent inhibitor of the enzymatic reaction involved in sugar nucleotide metabolism. UMPG was synthesized by chemical coupling of 2,3,4,6-tetra-O-acetyl-α-d-glucopyranosyl bromide with uridine 5′-monophosphate (UMP) to give uridine 5′-monophosphate 2″,3″,4″,6″-tetra-O-acetyl-α-d-glucose (UMPTAG), followed by deacetylation of UMPTAG with sodium methoxide. In addition to UMPG, UMPTAG showed potent inhibitory activity toward yeast UDPG pyrophosphorylase (UDPG synthetase). UMPG and UMPTAG were competitive with UDPG in the pyrophosphorolytic reaction, with inhibition constants (Ki) of 4.8 and 20.7 μM, respectively, but non-competitive with inorganic pyrophosphate. UMPG and UMPTAG also inhibited the enzyme non-competitively in the reverse reaction to synthesize UDPG from UTP and glucose 1-phosphate (G1P). The acetyl group of UMPTAG was thought to enhance its hydrophobic interaction, possibly with an active site region of the enzyme functional for binding with UDPG.