Synthesis and Enzymatic Studies of Isoprenoid Thiolo Bisubstrate Analogues
| Autor: | Gurusankar Ramamoorthy, Richard M. Phan, C. Dale Poulter |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Allylic rearrangement Double bond Stereochemistry Mixed type Catalysis Substrate Specificity Structure-Activity Relationship 03 medical and health sciences Hemiterpenes Organophosphorus Compounds Farnesyl diphosphate synthase X-Ray Diffraction Moiety Structure–activity relationship Enzyme Inhibitors chemistry.chemical_classification biology Terpenes Organic Chemistry Geranyltranstransferase Terpenoid Kinetics 030104 developmental biology Enzyme chemistry biology.protein |
| Zdroj: | The Journal of Organic Chemistry. 81:5093-5100 |
| ISSN: | 1520-6904 0022-3263 |
| DOI: | 10.1021/acs.joc.6b00664 |
| Popis: | Chain elongation prenyltransferases catalyze the addition of the hydrocarbon moiety of allylic isoprenoid diphosphates to the carbon-carbon double bond in isopentenyl diphosphate (IPP) in the primary building reactions in the isoprenoid biosynthetic pathway. Bis-O-diphosphate analogues 3-OPP/OPP, 4-OPP/OPP, and 5-OPP/OPP and bis-thiolodiphosphate bisubstrate analogues 3-SPP/SPP, 4-SPP/SPP, and 5-SPP/SPP were synthesized. The analogues 4-OPP/OPP, 5-OPP/OPP, 4-SPP/SPP, and 5-SPP/SPP were excellent competitive inhibitors of avian farnesyl diphosphate synthase with KI = 1.0 ± 0.12 μM, KI = 0.5 ± 0.2 μM, KI = 0.7 ± 0.3 μM, and KI = 2.9 ± 0.27 μM, respectively, whereas, analogues 3-OPP/OPP and 3-SPP/SPP displayed mixed type inhibition with KI = 1.4 μM and KI = 5.5 μM, respectively. |
| Databáze: | OpenAIRE |
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