Here we present a novel technique that utilizes a supporting inorganic film for MD simulations of flat-shaped DNA origami structures in explicit solvent. The number of atoms is typically over 16 million including water molecules. By utilizing a GPU capable simulation engine, we have addressed conformational changes of a DNA origami structure under normal ionic strength and deionized water conditions up to the order of one nanosecond simulation time. Our results demonstrate that DNA origami configuration undergoes a continual growth in the absence of cations, while it is not the case for normal ionic strength. Statistical analysis of helix forms for these DNA origami structures reveals that not only cations but also water permittivity contributed to the maintenance of B-DNA helix form during the stretching motion. These results will provide key features in designing molecular robots as assembly of DNA origami structural components such as scaffolds, connectors and channels.
{"title":"All-atom molecular dynamics of film supported flat-shaped DNA origami in water","authors":"R. Azuma, Sae Kishi, G. Gutmann, A. Konagaya","doi":"10.1273/CBIJ.18.96","DOIUrl":"https://doi.org/10.1273/CBIJ.18.96","url":null,"abstract":"Here we present a novel technique that utilizes a supporting inorganic film for MD simulations of flat-shaped DNA origami structures in explicit solvent. The number of atoms is typically over 16 million including water molecules. By utilizing a GPU capable simulation engine, we have addressed conformational changes of a DNA origami structure under normal ionic strength and deionized water conditions up to the order of one nanosecond simulation time. Our results demonstrate that DNA origami configuration undergoes a continual growth in the absence of cations, while it is not the case for normal ionic strength. Statistical analysis of helix forms for these DNA origami structures reveals that not only cations but also water permittivity contributed to the maintenance of B-DNA helix form during the stretching motion. These results will provide key features in designing molecular robots as assembly of DNA origami structural components such as scaffolds, connectors and channels.","PeriodicalId":40659,"journal":{"name":"Chem-Bio Informatics Journal","volume":"100 1","pages":""},"PeriodicalIF":0.3,"publicationDate":"2018-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80667387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In the cyclohexane derivatives, the equatorial conformer, having less steric repulsion of hydrogen atoms adjacent to substituent, is dominant over the axial conformer. This is a normal stereochemical requirement. In hexose, containing oxygen atoms in the ring, however, α-anomer (with axial substituent) is more stable than β-anomer (with equatorial substituent) and it is called the anomeric effect. Why does this phenomenon, which is not compatible with the stereochemical intuition (but still widely accepted), happen at all? It has been more than 60 years since Edward reported it, but the root cause has not yet become clear. At present, the most popular explanation for the anomeric effect is that it is due to the interaction between a lone pair of electrons on oxygen and the anti-bonding orbital (σ*) of C-R bond. Contrary to popular belief, we demonstrate that this explanation does not hold.
{"title":"The Orbital-Effect-Myth","authors":"M. Nishio, Yuji Kohno","doi":"10.1273/CBIJ.18.86","DOIUrl":"https://doi.org/10.1273/CBIJ.18.86","url":null,"abstract":"In the cyclohexane derivatives, the equatorial conformer, having less steric repulsion of hydrogen atoms adjacent to substituent, is dominant over the axial conformer. This is a normal stereochemical requirement. In hexose, containing oxygen atoms in the ring, however, α-anomer (with axial substituent) is more stable than β-anomer (with equatorial substituent) and it is called the anomeric effect. Why does this phenomenon, which is not compatible with the stereochemical intuition (but still widely accepted), happen at all? It has been more than 60 years since Edward reported it, but the root cause has not yet become clear. At present, the most popular explanation for the anomeric effect is that it is due to the interaction between a lone pair of electrons on oxygen and the anti-bonding orbital (σ*) of C-R bond. Contrary to popular belief, we demonstrate that this explanation does not hold.","PeriodicalId":40659,"journal":{"name":"Chem-Bio Informatics Journal","volume":"105 1","pages":""},"PeriodicalIF":0.3,"publicationDate":"2018-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80494839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Scientific objectivity was not a problem in the early days of molecular biology. However, relativism seems to have invaded some areas of the field, damaging the objectivity of its analyses. This review reports on the status of this issue by investigating a number of cases.
{"title":"Concerns regarding the deterioration of objectivity in molecular biology","authors":"T. Konishi","doi":"10.1273/CBIJ.18.173","DOIUrl":"https://doi.org/10.1273/CBIJ.18.173","url":null,"abstract":"Scientific objectivity was not a problem in the early days of molecular biology. However, relativism seems to have invaded some areas of the field, damaging the objectivity of its analyses. This review reports on the status of this issue by investigating a number of cases.","PeriodicalId":40659,"journal":{"name":"Chem-Bio Informatics Journal","volume":"42 1","pages":""},"PeriodicalIF":0.3,"publicationDate":"2018-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85355483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shintaro Ota, Shougo Tomioka, Haruki Sogawa, Riku Satou, Mitsuki Fujimori, P. A. Karpov, S. V. Shul'ga, Y. Blume, N. Kurita
Curcumin can bind to tubulin and inhibit the formation of tubulin polymer, which contributes to the formation of microtubule. Binding sites of curcumin on the αand β-tubulin heterodimer were predicted by a molecular docking study to ascertain probable causes for the observed anti-microtubule effects of curcumin. However, the specific interactions between curcumin and the tubulins have yet to be elucidated at an electronic level. We here investigated the binding properties between curcumin and αor β-tubulin of Plasmodium falciparum, using ab initio fragment molecular orbital (FMO) calculations, in order to reveal the preferable binding sites of curcumin on these tubulins. The results were compared with those for some microtubule destabilizing drugs evaluated by the same method to confirm the efficiency of curcumin as an inhibitor to the tubulins. Our ab initio FMO calculations might provide useful information for proposing novel therapeutic agents with significant binding affinity to both the αand β-tubulins.
{"title":"Binding properties between curcumin and malarial tubulin: molecular-docking and ab initio fragment molecular orbital calculations","authors":"Shintaro Ota, Shougo Tomioka, Haruki Sogawa, Riku Satou, Mitsuki Fujimori, P. A. Karpov, S. V. Shul'ga, Y. Blume, N. Kurita","doi":"10.1273/CBIJ.18.44","DOIUrl":"https://doi.org/10.1273/CBIJ.18.44","url":null,"abstract":"Curcumin can bind to tubulin and inhibit the formation of tubulin polymer, which contributes to the formation of microtubule. Binding sites of curcumin on the αand β-tubulin heterodimer were predicted by a molecular docking study to ascertain probable causes for the observed anti-microtubule effects of curcumin. However, the specific interactions between curcumin and the tubulins have yet to be elucidated at an electronic level. We here investigated the binding properties between curcumin and αor β-tubulin of Plasmodium falciparum, using ab initio fragment molecular orbital (FMO) calculations, in order to reveal the preferable binding sites of curcumin on these tubulins. The results were compared with those for some microtubule destabilizing drugs evaluated by the same method to confirm the efficiency of curcumin as an inhibitor to the tubulins. Our ab initio FMO calculations might provide useful information for proposing novel therapeutic agents with significant binding affinity to both the αand β-tubulins.","PeriodicalId":40659,"journal":{"name":"Chem-Bio Informatics Journal","volume":"8 1","pages":"44-57"},"PeriodicalIF":0.3,"publicationDate":"2018-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87779221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ryosuke Takeda, Rie Suzuki, Ittetsu Kobayashi, Kentaro Kawai, A. Kittaka, M. Takimoto-Kamimura, N. Kurita
The chirality of a compound affects its biochemical and pharmaceutical properties. It was found that the binding affinity between vitamin D receptor (VDR) and its ligand depends significantly on the chirality of the ligand. To elucidate the reason for this dependence, we here investigated the specific interactions between VDR and two types of ligands with different chirality, using ab initio fragment molecular orbital (FMO) calculations. The FMO results reveal that the part of ligand with different chirality interacts strongly with the imidazole ring of histidine side-chain in VDR, and that the binding affinity between VDR and the ligands depends on the protonation state of the histidine. This finding indicates the possibility that ligands with different chirality can assign the protonation state of VDR histidine residues existing near the ligand.
{"title":"Specific interactions between vitamin D receptor and ligand depending on its chirality: ab initio fragment molecular orbital calculations","authors":"Ryosuke Takeda, Rie Suzuki, Ittetsu Kobayashi, Kentaro Kawai, A. Kittaka, M. Takimoto-Kamimura, N. Kurita","doi":"10.1273/CBIJ.18.32","DOIUrl":"https://doi.org/10.1273/CBIJ.18.32","url":null,"abstract":"The chirality of a compound affects its biochemical and pharmaceutical properties. It was found that the binding affinity between vitamin D receptor (VDR) and its ligand depends significantly on the chirality of the ligand. To elucidate the reason for this dependence, we here investigated the specific interactions between VDR and two types of ligands with different chirality, using ab initio fragment molecular orbital (FMO) calculations. The FMO results reveal that the part of ligand with different chirality interacts strongly with the imidazole ring of histidine side-chain in VDR, and that the binding affinity between VDR and the ligands depends on the protonation state of the histidine. This finding indicates the possibility that ligands with different chirality can assign the protonation state of VDR histidine residues existing near the ligand.","PeriodicalId":40659,"journal":{"name":"Chem-Bio Informatics Journal","volume":"17 1","pages":"32-43"},"PeriodicalIF":0.3,"publicationDate":"2018-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72869641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Y. Yagi, Takatomo Kimura, M. Kamezawa, Y. Naoshima
We are presently continuing to perform biomolecular chemical simulations for Burkholderia cepacia lipase (BCL) and Candida antarctica lipase typeB (CALB) to predict their enantioselectivity and reactivity toward various organic compounds. Here, we describe molecular dynamics (MD) and fragment molecular orbital (FMO) calculations on the complexes of CALB with primary and secondary alcohol esters. For esters with high enantioselectivity, the fast-reacting enantiomer of esters is located near the active site of CALB, whereas the slow-reacting enantiomer of esters moves away from the active site of CALB. On the other hand, for the esters with low enantioselectivity, we found that both (R)and (S)-enantiomers of esters remain the active site of CALB. The FMO computations indicate that for the esters with high enantioselectivity, each fast-reacting enantiomer shows strong interactions with some particular amino acid residues, including Thr40, whereas for the esters with low enantioselectivity, both (R)and (S)-enantiomers interact with identical amino acid residues including Thr40. It is predictable that Thr40 in CALB plays an important role in the chiral recognition of enantiomers through lipase-catalyzed biotransformations.
{"title":"Biomolecular Chemical Simulations toward Elucidation of the Enantioselectivity and Reactivity of Lipases in Organic Synthesis","authors":"Y. Yagi, Takatomo Kimura, M. Kamezawa, Y. Naoshima","doi":"10.1273/CBIJ.18.21","DOIUrl":"https://doi.org/10.1273/CBIJ.18.21","url":null,"abstract":"We are presently continuing to perform biomolecular chemical simulations for Burkholderia cepacia lipase (BCL) and Candida antarctica lipase typeB (CALB) to predict their enantioselectivity and reactivity toward various organic compounds. Here, we describe molecular dynamics (MD) and fragment molecular orbital (FMO) calculations on the complexes of CALB with primary and secondary alcohol esters. For esters with high enantioselectivity, the fast-reacting enantiomer of esters is located near the active site of CALB, whereas the slow-reacting enantiomer of esters moves away from the active site of CALB. On the other hand, for the esters with low enantioselectivity, we found that both (R)and (S)-enantiomers of esters remain the active site of CALB. The FMO computations indicate that for the esters with high enantioselectivity, each fast-reacting enantiomer shows strong interactions with some particular amino acid residues, including Thr40, whereas for the esters with low enantioselectivity, both (R)and (S)-enantiomers interact with identical amino acid residues including Thr40. It is predictable that Thr40 in CALB plays an important role in the chiral recognition of enantiomers through lipase-catalyzed biotransformations.","PeriodicalId":40659,"journal":{"name":"Chem-Bio Informatics Journal","volume":"44 1","pages":"21-31"},"PeriodicalIF":0.3,"publicationDate":"2018-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82825440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Adverse effects induced by the duplication of drugs with anticholinergic effects are a problem among elderly people who take many drugs. Various anticholinergic rating scales have been published and are applied clinically to evaluate a patient’s anticholinergic burden; however, there are some problems with these scales, such as drugs that are assessed differently between scales. We aimed to construct a method to more correctly distinguish between drugs with and without anticholinergic effects and to understand the properties of drugs that have anticholinergic effects. We constructed a model for identifying anticholinergic effects via a decision tree, using descriptors indicating the physicochemical properties of the drugs. The best split yielded a decision tree with 46 branches (area under the receiver operating characteristic curve = 0.99). However, only seven branches, defined by six descriptors: ASA_P, GCUT_PEOE_0, opr_brigid, PEOE_VSA+1, GCUT_SLOGP_0, vsa_pol (related to van der Waals surface areas, partial charges, and molecule structures), were required to identify drugs with anticholinergic effects. This result suggests a relationship between the hydrophobic interactions of drugs and the muscarinic receptor. In this study, we constructed a model to predict whether drugs have anticholinergic effects, and obtained essential physicochemical information on the drugs to distinguish their anticholinergic effects. It is our hope that these findings provide useful information for predicting anticholinergic effects of drugs in clinical
{"title":"Analysis of physicochemical properties of drugs included in anticholinergic rating scales","authors":"Junko Nagai, H. Kagaya, Y. Uesawa","doi":"10.1273/CBIJ.18.1","DOIUrl":"https://doi.org/10.1273/CBIJ.18.1","url":null,"abstract":"Adverse effects induced by the duplication of drugs with anticholinergic effects are a problem among elderly people who take many drugs. Various anticholinergic rating scales have been published and are applied clinically to evaluate a patient’s anticholinergic burden; however, there are some problems with these scales, such as drugs that are assessed differently between scales. We aimed to construct a method to more correctly distinguish between drugs with and without anticholinergic effects and to understand the properties of drugs that have anticholinergic effects. We constructed a model for identifying anticholinergic effects via a decision tree, using descriptors indicating the physicochemical properties of the drugs. The best split yielded a decision tree with 46 branches (area under the receiver operating characteristic curve = 0.99). However, only seven branches, defined by six descriptors: ASA_P, GCUT_PEOE_0, opr_brigid, PEOE_VSA+1, GCUT_SLOGP_0, vsa_pol (related to van der Waals surface areas, partial charges, and molecule structures), were required to identify drugs with anticholinergic effects. This result suggests a relationship between the hydrophobic interactions of drugs and the muscarinic receptor. In this study, we constructed a model to predict whether drugs have anticholinergic effects, and obtained essential physicochemical information on the drugs to distinguish their anticholinergic effects. It is our hope that these findings provide useful information for predicting anticholinergic effects of drugs in clinical","PeriodicalId":40659,"journal":{"name":"Chem-Bio Informatics Journal","volume":"30 16 1","pages":"1-9"},"PeriodicalIF":0.3,"publicationDate":"2018-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82997246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Professor Toshio Fujita (1929-2017) as a pioneer of medicinal chemistry","authors":"T. Ishikawa, K. Yuta, Y. Tada, A. Konagaya","doi":"10.1273/CBIJ.17.110","DOIUrl":"https://doi.org/10.1273/CBIJ.17.110","url":null,"abstract":"","PeriodicalId":40659,"journal":{"name":"Chem-Bio Informatics Journal","volume":"61 1","pages":"110-111"},"PeriodicalIF":0.3,"publicationDate":"2017-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81130947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Asuka Hatabu, M. Harada, Yoshitake Takahashi, Shunsuke Watanabe, Kenya Sakamoto, Kousuke Okamoto, N. Kawashita, Yu-Shi Tian, T. Takagi
Alzheimer's disease (AD) and Parkinson's disease (PD) are both prominent central nervous system diseases that are frequently diagnosed and studied using brain single-photon emission computed tomography (SPECT). Owing to divergent clinical features, AD and PD are often considered distinct diseases; however, it is difficult to distinguish AD from PD on SPECT. Tools for objectively analyzing differences between AD and PD on SPECT images are not currently available. To construct a model for discriminating AD from PD in Japanese patients, we used a support vector machine (SVM) and SPECT images acquired at two different time points after radiotracer injection to extract the determinant regions for classification. We assessed SPECT images from 68 Japanese patients with AD or PD. After pre-processing noise voxels, a non-linear SVM classification with Gaussian kernels was adopted to construct the predictive model. The best SVM model was highly accurate for distinguishing AD from PD. The accuracy of this model was 98.1% for leave-one-out cross-validation and 78.6% for the test set. Our data showed that the temporal, sub-lobar, parietal, limbic, and frontal areas exhibited decreased regional cerebral blood flow in AD; whereas the frontal, anterior, parietal, and occipital areas exhibited decreased regional cerebral blood flow in PD. Here, we present a useful SVM model for classifying AD versus PD using SPECT images and show the utility of two-time-point SPECT imaging for AD/PD discrimination.
{"title":"Classification of Alzheimer’s disease and Parkinson’s disease using a support vector machine and probabilistic outputs","authors":"Asuka Hatabu, M. Harada, Yoshitake Takahashi, Shunsuke Watanabe, Kenya Sakamoto, Kousuke Okamoto, N. Kawashita, Yu-Shi Tian, T. Takagi","doi":"10.1273/CBIJ.17.112","DOIUrl":"https://doi.org/10.1273/CBIJ.17.112","url":null,"abstract":"Alzheimer's disease (AD) and Parkinson's disease (PD) are both prominent central nervous system diseases that are frequently diagnosed and studied using brain single-photon emission computed tomography (SPECT). Owing to divergent clinical features, AD and PD are often considered distinct diseases; however, it is difficult to distinguish AD from PD on SPECT. Tools for objectively analyzing differences between AD and PD on SPECT images are not currently available. To construct a model for discriminating AD from PD in Japanese patients, we used a support vector machine (SVM) and SPECT images acquired at two different time points after radiotracer injection to extract the determinant regions for classification. We assessed SPECT images from 68 Japanese patients with AD or PD. After pre-processing noise voxels, a non-linear SVM classification with Gaussian kernels was adopted to construct the predictive model. The best SVM model was highly accurate for distinguishing AD from PD. The accuracy of this model was 98.1% for leave-one-out cross-validation and 78.6% for the test set. Our data showed that the temporal, sub-lobar, parietal, limbic, and frontal areas exhibited decreased regional cerebral blood flow in AD; whereas the frontal, anterior, parietal, and occipital areas exhibited decreased regional cerebral blood flow in PD. Here, we present a useful SVM model for classifying AD versus PD using SPECT images and show the utility of two-time-point SPECT imaging for AD/PD discrimination.","PeriodicalId":40659,"journal":{"name":"Chem-Bio Informatics Journal","volume":"6 1","pages":"112-124"},"PeriodicalIF":0.3,"publicationDate":"2017-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78498277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ayano Kakiuchi, Shion Ito, S. Okuyama, Y. Furukawa, T. Mizuma
3, 5, 6, 7, 8, 3’, 4’-heptamethoxyflavone (HMF), which is present in citrus fruits, has been reported to induce brain-derived neurotropic factor (BDNF) production, and have an anti-inflammatory effect. However, its pharmacokinetics is obscure. Therefore, as the first study of HMF pharmacokinetics, the reversible binding of HMF to human serum albumin (HSA) has been examined. For the binding examination and further pharmacokinetic study of HMF, a simple HPLC assay method was established first. The HPLC system equipped with a UV detector (HPLC-UV) and an isocratic mobile phase were used. The accuracy of intra-assay validation at each concentration from 1 to 100 M was from 97.2 to 101.6%, and the precision of intra-assay validation was less than 1.60%. For inter-assay validation, the accuracy was from 97.1 to 104.5%, and the precision was less than 2.24% from 1 to 100 M of HMF. The reversible binding of HMF to HSA was performed by the equilibrium dialysis method. The bound fraction of HMF to 4.6% HSA decreased from around 70% to 55% as the total concentration of HMF increased. This concentration dependency of the reversible binding suggests that HMF may have a specific binding site on the HSA molecule. The HPLC method established in this study is now being used for further investigation of HMF pharmacokinetics, such as intestinal absorption.
{"title":"Human serum albumin binding of 3, 5, 6, 7, 8, 3’, 4’- heptamethoxyflavone, a citrus flavonoid possessing a neuroprotective effect","authors":"Ayano Kakiuchi, Shion Ito, S. Okuyama, Y. Furukawa, T. Mizuma","doi":"10.1273/CBIJ.17.103","DOIUrl":"https://doi.org/10.1273/CBIJ.17.103","url":null,"abstract":"3, 5, 6, 7, 8, 3’, 4’-heptamethoxyflavone (HMF), which is present in citrus fruits, has been reported to induce brain-derived neurotropic factor (BDNF) production, and have an anti-inflammatory effect. However, its pharmacokinetics is obscure. Therefore, as the first study of HMF pharmacokinetics, the reversible binding of HMF to human serum albumin (HSA) has been examined. For the binding examination and further pharmacokinetic study of HMF, a simple HPLC assay method was established first. The HPLC system equipped with a UV detector (HPLC-UV) and an isocratic mobile phase were used. The accuracy of intra-assay validation at each concentration from 1 to 100 M was from 97.2 to 101.6%, and the precision of intra-assay validation was less than 1.60%. For inter-assay validation, the accuracy was from 97.1 to 104.5%, and the precision was less than 2.24% from 1 to 100 M of HMF. The reversible binding of HMF to HSA was performed by the equilibrium dialysis method. The bound fraction of HMF to 4.6% HSA decreased from around 70% to 55% as the total concentration of HMF increased. This concentration dependency of the reversible binding suggests that HMF may have a specific binding site on the HSA molecule. The HPLC method established in this study is now being used for further investigation of HMF pharmacokinetics, such as intestinal absorption.","PeriodicalId":40659,"journal":{"name":"Chem-Bio Informatics Journal","volume":"197 1","pages":"103-109"},"PeriodicalIF":0.3,"publicationDate":"2017-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75924076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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