An Efficient One‐Pot Enzymatic Synthesis of Cardiac Glycosides with Varied Sugar Chain Lengths

Abstract

An efficient one‐pot enzymatic synthesis of cardiac glycosides with varied sugar chain lengths (average yield >80%) was carried out through sequential glycosylation using a steroid glycosyltransferase UGT74AN3 from Catharanthus roseus and a cyclodextrin glycosyltransferase from Bacillus licheniformis. A series of cardiac glycosides were obtained and showed enhanced affinity and selectivity for inhibition of the α2 isoform of Na+/K+‐ATPase. These findings demonstrate the significant potential of the one‐pot biocatalytic approach in the synthesis of diverse cardiac glycosides as potentially safer cardiotonic agents.

Enzymatic Synthesis of Puerarin Glucosides Using Cyclodextrin Glucanotransferase with Enhanced Antiosteoporosis Activity

“…Compared to PU-G , the glucoside with three sugar moieties ( PU-2G ) and the glucoside with four sugar moieties ( PU-3G ) were less potent, indicating that two sugar units are optimal for both the ALP activity and the expression of runx2. This is consistent with our previous results that the drug with an appropriate sugar chain length has the strongest activity . Recently, pharmacokinetic parameter analysis revealed that the PU- glycosylated compounds were absorbed more efficiently than the original compounds .…”

“…This is consistent with our previous results that the drug with an appropriate sugar chain length has the strongest activity. 32 Recently, pharmacokinetic parameter analysis revealed that the PU-glycosylated compounds were absorbed more efficiently than the original compounds. 47 These results indicate that these high solubilities of transglycosylation products can be used as a substitute for PU.…”

“…X15752.1) was overexpressed and purified as previously described by our group (Figure S1). 32 Cell counting kit-8 was obtained from Dojindo Laboratories (Dojindo, Japan). Alkaline phosphatase (ALP) detection kit was bought from Jiancheng Bioengineering Institute (Nanjing, China).…”

An Efficient Strategy for the Chemo‐Enzymatic Synthesis of Bufalin Glycosides with Improved Water Solubility and Inhibition against Na+, K+‐ATPase

“…[5,6] Glycosylation modification can enhance the water solubility, [7] targeting [8] and reduce the toxic and side effects of drugs. [9] Both chemical method [10] and enzymatic method [11] can achieve glycosylation, but enzymatic glycosylation has the advantages of green and high efficiency, [12] and thus its application is increasingly widespread. This article intends to modify bufalin via the chemo-enzymatic strategy.…”

“…But clinical application of bufalin is limited due to poor water solubility and large toxic side effects [5,6] . Glycosylation modification can enhance the water solubility, [7] targeting [8] and reduce the toxic and side effects of drugs [9] . Both chemical method [10] and enzymatic method [11] can achieve glycosylation, but enzymatic glycosylation has the advantages of green and high efficiency, [12] and thus its application is increasingly widespread.…”