1. Stereoselective Bioreduction of α-diazo-β-keto Esters
Sergio González-Granda, Taíssa A Costin, Marcus M Sá, Vicente Gotor-Fernández Molecules. 2020 Feb 19;25(4):931.doi: 10.3390/molecules25040931.
Diazo compounds are versatile reagents in chemical synthesis and biology due to the tunable reactivity of the diazo functionality and its compatibility with living systems. Much effort has been made in recent years to explore their accessibility and synthetic potential; however, their preparation through stereoselective enzymatic asymmetric synthesis has been scarcely reported in the literature. Alcohol dehydrogenases (ADHs, also called ketoreductases, KREDs) are powerful redox enzymes able to reduce carbonyl compounds in a highly stereoselective manner. Herein, we have developed the synthesis and subsequent bioreduction of nine α-diazo-β-keto esters to give optically active α-diazo-β-hydroxy esters with potential applications as chiral building blocks in chemical synthesis. Therefore, the syntheses of prochiral α-diazo-β-keto esters bearing different substitution patterns at the adjacent position of the ketone group (N3CH2, ClCH2, BrCH2, CH3OCH2, NCSCH2, CH3, and Ph) and in the alkoxy portion of the ester functionality (Me, Et, and Bn), were carried out through the diazo transfer reaction to the corresponding β-keto esters in good to excellent yields (81-96%). After performing the chemical reduction of α-diazo-β-keto esters with sodium borohydride and developing robust analytical conditions to monitor the biotransformations, their bioreductions were exhaustively studied using in-house made Escherichia coli overexpressed and commercially available KREDs. Remarkably, the corresponding α-diazo-β-hydroxy esters were obtained in moderate to excellent conversions (60 to >99%) and high selectivities (85 to >99% ee) after 24 h at 30 °C. The best biotransformations in terms of conversion and enantiomeric excess were successfully scaled up to give the expected chiral alcohols with almost the same activity and selectivity values observed in the enzyme screening experiments.
2. Dual-functionalized hyaluronic acid as a facile modifier to prepare polyanionic collagen
Min Zhang, Junhui Yang, Feng Deng, Chenchen Guo, Qili Yang, Hui Wu, Yonghao Ni, Liulian Huang, Lihui Chen, Cuicui Ding Carbohydr Polym. 2019 Jul 1;215:358-365.doi: 10.1016/j.carbpol.2019.03.086.Epub 2019 Mar 29.
Hyaluronic acid (HA) is a natural polysaccharide possesses outstanding physiological activities. In this work, HA was activated as a novel collagen modifier via the esterification reaction between N-hydroxysuccinimide (NHS) and the carboxyl groups of HA. Both of Fourier transform infrared spectroscopy (FTIR) and 1H- nuclear magnetic resonance (NMR) spectra indicated the successful synthesis of HA-NHS esters. As reflected by FTIR, circular dichroism (CD) and sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE), collagens modified with HA-NHS ester maintained its intact triplex structure with larger molecular weight. The resultant polyanionic collagen displayed an excellent dissolubility in the neutral water to form a clear solution, due to the significantly lower isoelectric point values (3.8-4.4) compared with that of the native collagen (7.1). In addition, the thermal transition temperature of collagen was significantly increased (16 °C) after modifying with HA-NHS esters. Both of the aggregation morphology and rheological property exhibited high dependence on the NHS/COOH ratio of HA-NHS esters, as reflected by field-emission scanning electron microscopy (FESEM) and rheological test, respectively. The present study offered a novel dual-functional modifier based on the design of HA-NHS ester to obtain water-soluble collagen with desired thermal stability and rheological property, which will significantly widen the application range of collagen, especially in the fields of injectable biodegradable materials and cosmetics.
3. Stability and bioavailability of protein matrix-encapsulated astaxanthin ester microcapsules
Lu Yang, Fei Li, Xinyu Cao, Xing Qiao, Changhu Xue, Jie Xu J Sci Food Agric. 2022 Mar 30;102(5):2144-2152.doi: 10.1002/jsfa.11556.Epub 2021 Oct 18.
Background:Astaxanthin ester derived from Haematococcus pluvialis is often used as a functional and nutritional ingredient in foods. However, its utilization is currently limited as a result of its chemical instability and low bioavailability. Food matrix microcapsules are becoming increasingly popular because of their safety and high encapsulation efficiency. In the present study, the effect of protein matrixes on the properties of microcapsules was evaluated. Results:We investigated the effects of storage on astaxanthin ester microcapsules and the corresponding rehydration solution at 40 °C under a nitrogen atmosphere, as well as in darkness. The results showed that the stability of products prepared based on whey protein (WP) and corn-gluten was superior to that of products prepared based on lactoferrin, soy protein and sodium caseinate. The bioavailability of astaxanthin ester microcapsules encapsulated with different proteins and examined by means of astaxanthin concentrations in the serum and liver after oral administration was compared. All five protein wall materials could significantly improve the bioavailability of astaxanthin ester. The microcapsules prepared based on WP had the highest bioavailability, with a value of 10.69 ± 0.75 μg·h mL-1 , which was 3.15 times higher compared to that of the control group.Conclusion:The results of the present study showed that protein encapsulation, especially WP encapsulation, could effectively improve the stability, water solubility and bioavailability of astaxanthin esters. Thus, WP can be used as the main wall material in delivery systems. © 2021 Society of Chemical Industry.
