Aziridine derivatives of N^5-methyltetrahydrofolate were designed and synthesized based on the mechanism of methionine synthase, and their biological activities were investigated as well. The aziridine derivatives 1 a...Aziridine derivatives of N^5-methyltetrahydrofolate were designed and synthesized based on the mechanism of methionine synthase, and their biological activities were investigated as well. The aziridine derivatives 1 and 6 exhibited superior inhibitory activities（IC50：5.05 and 4.15 μmol/L, respectively） compared to the corresponding chain analogue 4（IC55=24.42 μmol/L）. The results suggest that the aziridine derivatives can get potential activities against nucleophilic methionine synthase.展开更多
Among the folate compounds, 5-methyltetrahydrofolic acid (5-CH3THF) is regarded as one of the most bioactive forms of folate. It is regarded as the better source of folate to humans as compared to folic acid, a synthe...Among the folate compounds, 5-methyltetrahydrofolic acid (5-CH3THF) is regarded as one of the most bioactive forms of folate. It is regarded as the better source of folate to humans as compared to folic acid, a synthetic form of folate, which is used for fortifying foods to prevent the incidence of neural tube defects in the new born babies. The use of 5-CH3THF as an alternative fortificant, in place of folic acid, has been explored by various researchers. However, fortification of 5-CH3THF is problematic due to its lower stability. This study investigated the stability of microencapsulated 5-CH3THF in biscuits baked at various temperatures and times as well as changes in their physical properties. Microcapsule with pectin and alginate ratio of 80:20, prepared by spray drying, gave the highest retention (68.6%) of the 5-CH3THF, therefore, chosen for fortification. The encapsulated and unencapsulated 5-CH3THF were mixed separately with flour and biscuit ingredients and baked at 180℃, 200 and 220℃, each for 5, 9 and 12 min. The inclusion of encapsulated and unencapsulated 5-CH3THF in the biscuit formulation and subsequent baking at various temperatures and times resulted in retention of 5-CH3THF from 19.1% to 1.7%. Microencapsulation of 5-CH3THF slightly improved the retention of 5-CH3THF over unencapsuated biscuits at 180℃ for 5 min, but almost no such effect was achieved under baking temperatures of 200℃ and 220℃. Physical analysis showed darker colour, harder texture and lower moisture content for biscuits baked at higher test temperatures. It seems intense heating condition that caused “over baking” of the biscuit likely to be responsible for the loss of the vitamin as well as less desirable physical properties of the biscuits.展开更多
A sensitive method based on high-performance liquid chromatography-tandem mass spectrometry （LC- MS/MS） has been developed for the simultaneous determination of folic acid （FA） and its active meta- bolite, 5-methy...A sensitive method based on high-performance liquid chromatography-tandem mass spectrometry （LC- MS/MS） has been developed for the simultaneous determination of folic acid （FA） and its active meta- bolite, 5-methyltetrahydrofolic acid （5-M-THF）, in human plasma. The analytes were extracted from plasma with methanol solution containing 10 mg/mL of 2-mercaptoethanol and 0.025% （v/v） ammonium hydroxide. FA and 5-M-THF were more stable after the addition of 2-mercaptoethanol and ammonium hydroxide in the sample preparation procedures of this study than they were in the previously published methods. Chromatographic separation was performed on a Hedera ODS-2 column using a gradient elution system of acetonitrile and 1 mM ammonium acetate buffer solution containing 0.6% formic acid as mobile phase. LC-MS/MS was carried out with an ESI ion-source and operated in the multiple reaction monitoring （MRM） mode. The assay was linear over the concentration ranges of 0.249-19.9 ng/mL for FA, and 5.05-50.5 ng/mL for 5-M-THF. The developed LC-MS/MS method offers increased sensitivity for quantification of FA and 5-M-THF in human plasma and was applicable to a pharmacokinetic study of FA and 5-M-THF.展开更多
Objectives:Folates are B vitamins that are essential for several molecular,cellular,and biological processes,including nucleotide synthesis,methylation,and methionine cycling.The physiological impacts of these process...Objectives:Folates are B vitamins that are essential for several molecular,cellular,and biological processes,including nucleotide synthesis,methylation,and methionine cycling.The physiological impacts of these processes on health also extend to cell proliferation,folate deficiency anemia,and reduction of the risk of birth defects during pregnancy.The primary objective of this study was to characterize the binding affinities of different folate forms,folic acid(FA),5-methyltetrahydrofolate(5MTHF),and folinic acid,to the folate receptorsαandβ,and to the bovine milk folate binding protein.These three dietary forms of folate are found in enriched grains(FA),various fruits and leafy vegetables(folinic acid),and red blood cells(5MTHF).Methods:The half maximal inhibitory concentration values and binding curves of each of these folates for each receptor were determined.Results:Our results indicated that FA had the highest affinity for all folate receptors,followed by 5MTHF,and lastly,by folinic acid,examined by several orders of magnitudes.Conclusion:These data are expected to provide new insights into the therapeutic applications of the different forms of folate in a variety of diseases.展开更多
基金Supported by the National Natural Science Foundation of China（No.21172014）.
文摘Aziridine derivatives of N^5-methyltetrahydrofolate were designed and synthesized based on the mechanism of methionine synthase, and their biological activities were investigated as well. The aziridine derivatives 1 and 6 exhibited superior inhibitory activities（IC50：5.05 and 4.15 μmol/L, respectively） compared to the corresponding chain analogue 4（IC55=24.42 μmol/L）. The results suggest that the aziridine derivatives can get potential activities against nucleophilic methionine synthase.
文摘Among the folate compounds, 5-methyltetrahydrofolic acid (5-CH3THF) is regarded as one of the most bioactive forms of folate. It is regarded as the better source of folate to humans as compared to folic acid, a synthetic form of folate, which is used for fortifying foods to prevent the incidence of neural tube defects in the new born babies. The use of 5-CH3THF as an alternative fortificant, in place of folic acid, has been explored by various researchers. However, fortification of 5-CH3THF is problematic due to its lower stability. This study investigated the stability of microencapsulated 5-CH3THF in biscuits baked at various temperatures and times as well as changes in their physical properties. Microcapsule with pectin and alginate ratio of 80:20, prepared by spray drying, gave the highest retention (68.6%) of the 5-CH3THF, therefore, chosen for fortification. The encapsulated and unencapsulated 5-CH3THF were mixed separately with flour and biscuit ingredients and baked at 180℃, 200 and 220℃, each for 5, 9 and 12 min. The inclusion of encapsulated and unencapsulated 5-CH3THF in the biscuit formulation and subsequent baking at various temperatures and times resulted in retention of 5-CH3THF from 19.1% to 1.7%. Microencapsulation of 5-CH3THF slightly improved the retention of 5-CH3THF over unencapsuated biscuits at 180℃ for 5 min, but almost no such effect was achieved under baking temperatures of 200℃ and 220℃. Physical analysis showed darker colour, harder texture and lower moisture content for biscuits baked at higher test temperatures. It seems intense heating condition that caused “over baking” of the biscuit likely to be responsible for the loss of the vitamin as well as less desirable physical properties of the biscuits.
文摘A sensitive method based on high-performance liquid chromatography-tandem mass spectrometry （LC- MS/MS） has been developed for the simultaneous determination of folic acid （FA） and its active meta- bolite, 5-methyltetrahydrofolic acid （5-M-THF）, in human plasma. The analytes were extracted from plasma with methanol solution containing 10 mg/mL of 2-mercaptoethanol and 0.025% （v/v） ammonium hydroxide. FA and 5-M-THF were more stable after the addition of 2-mercaptoethanol and ammonium hydroxide in the sample preparation procedures of this study than they were in the previously published methods. Chromatographic separation was performed on a Hedera ODS-2 column using a gradient elution system of acetonitrile and 1 mM ammonium acetate buffer solution containing 0.6% formic acid as mobile phase. LC-MS/MS was carried out with an ESI ion-source and operated in the multiple reaction monitoring （MRM） mode. The assay was linear over the concentration ranges of 0.249-19.9 ng/mL for FA, and 5.05-50.5 ng/mL for 5-M-THF. The developed LC-MS/MS method offers increased sensitivity for quantification of FA and 5-M-THF in human plasma and was applicable to a pharmacokinetic study of FA and 5-M-THF.
文摘Objectives:Folates are B vitamins that are essential for several molecular,cellular,and biological processes,including nucleotide synthesis,methylation,and methionine cycling.The physiological impacts of these processes on health also extend to cell proliferation,folate deficiency anemia,and reduction of the risk of birth defects during pregnancy.The primary objective of this study was to characterize the binding affinities of different folate forms,folic acid(FA),5-methyltetrahydrofolate(5MTHF),and folinic acid,to the folate receptorsαandβ,and to the bovine milk folate binding protein.These three dietary forms of folate are found in enriched grains(FA),various fruits and leafy vegetables(folinic acid),and red blood cells(5MTHF).Methods:The half maximal inhibitory concentration values and binding curves of each of these folates for each receptor were determined.Results:Our results indicated that FA had the highest affinity for all folate receptors,followed by 5MTHF,and lastly,by folinic acid,examined by several orders of magnitudes.Conclusion:These data are expected to provide new insights into the therapeutic applications of the different forms of folate in a variety of diseases.
