Chemical & pharmaceutical bulletin最新文献_第10页

Spectral and HPLC Analyses of Synthesized Butin and Butein. 合成丁素和丁素的光谱和 HPLC 分析。

IF 1.5 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2024-01-01 DOI: 10.1248/cpb.c24-00239

Takashi Kamei, Jun Miyazaki, Ryoga Hori, Hiroaki Saito, Tatsuo Takahashi, Ken-Ichi Shinohara, Masakazu Miura, Hirokazu Suzuki

{"title":"Spectral and HPLC Analyses of Synthesized Butin and Butein.","authors":"Takashi Kamei, Jun Miyazaki, Ryoga Hori, Hiroaki Saito, Tatsuo Takahashi, Ken-Ichi Shinohara, Masakazu Miura, Hirokazu Suzuki","doi":"10.1248/cpb.c24-00239","DOIUrl":"https://doi.org/10.1248/cpb.c24-00239","url":null,"abstract":"Butin and butein are significant bioactive flavanones derived from plants, existing as tautomers of each other. However, their physicochemical attributes, such as their spectral profiles under varying experimental conditions in aqueous solutions and established chromatographic methods for distinguishing between them, remain undetermined. In this study, we determined the basic properties of butin and butein using conventional spectroscopic, reversed-phase, and chiral HPLC analyses. The spectra of the synthesized butin and butein were analyzed using a UV-Vis spectrophotometer in several solvents with different polarities as well as in aqueous solutions at various pH values. Furthermore, the behavior of the measured spectra was reproduced by calculations to reveal the effects of the solvent and pH on the spectra of butin and butein in organic and aqueous solutions. Subsequently, we assessed the structural stability of butin and butein using reversed-phase HPLC, which revealed that butein is unstable compared with butin in a general culture medium. The synthesized butin was effectively separated into R- and S-isomers with positive and negative Cotton effects, respectively, via HPLC using a chiral column. These findings will aid in uncovering the individual properties of both butin and butein that may have been concealed by their tautomerism and enable the synthesis of S-butin, which is typically challenging and time-consuming to isolate.","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141554227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Neuroimmune Dysfunction in Alzheimer's Disease and Other Forms of Dementia. 阿尔茨海默病和其他形式痴呆症的神经免疫功能障碍

IF 1.5 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2024-01-01 DOI: 10.1248/cpb.c23-00464

Takuya Yamane, Takeshi Yoshioka, Yusuke Shimo

{"title":"Neuroimmune Dysfunction in Alzheimer's Disease and Other Forms of Dementia.","authors":"Takuya Yamane, Takeshi Yoshioka, Yusuke Shimo","doi":"10.1248/cpb.c23-00464","DOIUrl":"https://doi.org/10.1248/cpb.c23-00464","url":null,"abstract":"Alzheimer's disease (AD) is a common form of dementia. Although the causal mechanisms of AD are not fully understood, intracerebral accumulation of amyloid beta (Aβ) and tau aggregates seems to play an important role in disease development. Therefore, numerous experimental and clinical studies targeting the Aβ and tau proteins have been performed. However, these treatments have not achieved good clinical results. Additionally, recent findings have indicated that immune abnormalities contribute to the pathogenesis of AD. Several immune- and microglia-related genes have been identified as putative causative genes for the disease. Microglia, which are resident immune cells in the central nervous system (CNS), are key players that maintain brain homeostasis by communicating with other cells, such as astrocytes and immune cells, in or around the CNS. Furthermore, dysfunction of microglia and the immune system of the CNS could lead to chronic neuroinflammation and impairment of protective neuroimmune responses, which have been associated with the pathogenesis of AD and other forms of dementia. In this review, we assemble information regarding genetic evidence, imaging and biofluid biomarkers, and the pathophysiology of AD, especially highlighting bilateral (protective or detrimental) microglial functions, thus connecting neuroimmune dysfunction and AD. We also introduce candidate drugs to target neuroimmune dysfunction in AD. Finally, we discuss future therapeutic precision medicine approaches for AD, which could be achieved by identifying and targeting signals critical for AD pathogenesis through analyses of interactions between genetic risk factors, as well as identifying and modulating disease-relevant immune cell populations.","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141466476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Epigenetic Inhibitors as Alzheimer's Disease Therapeutic Agents. 表观遗传抑制剂作为阿尔茨海默病治疗药物。

IF 1.5 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2024-01-01 DOI: 10.1248/cpb.c23-00027

Yasunobu Yamashita, Yukihiro Itoh, Yuri Takada, Takayoshi Suzuki

{"title":"Epigenetic Inhibitors as Alzheimer's Disease Therapeutic Agents.","authors":"Yasunobu Yamashita, Yukihiro Itoh, Yuri Takada, Takayoshi Suzuki","doi":"10.1248/cpb.c23-00027","DOIUrl":"https://doi.org/10.1248/cpb.c23-00027","url":null,"abstract":"Alzheimer's disease (AD) is the leading cause of senile dementia, and the rapid increase in the frequency of AD cases has been attributed to population aging. However, current drugs have difficulty adequately suppressing symptoms and there is still a medical need for symptomatic agents. On the other hand, it has recently become clear that epigenetic dysfunctions are deeply involved in the development of cognitive impairments. Therefore, epigenetics-related proteins have attracted much attention as drug targets for AD. Early-developed epigenetic inhibitors were inappropriate for AD treatment because of their limited potential for oral administration, blood-brain barrier penetration, high target selectivity, and sufficient dose-limiting toxicity which are essential properties for small molecule drugs targeting chronic neurodegenerative diseases such as AD. In recent years, drug discovery studies have been actively performed to overcome such problems and several novel inhibitors targeting the epigenetics-related proteins are of interest as promising AD therapeutic agents. Here, we review the small molecule inhibitors of histone deacetylase (HDAC), lysine-specific demethylase 1 (LSD1) or bromodomains and extra-terminal domain (BET) protein, that enable memory function improvement in AD model mice.","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141466473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dissolution Profiles of Oral Disintegrating Tablet with Taste Masking Granule Polymer Coating in Biorelevant Bicarbonate Buffer. 带有掩味颗粒聚合物涂层的口腔崩解片在生物相关碳酸氢盐缓冲液中的溶解曲线

IF 1.7 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2024-01-01 DOI: 10.1248/cpb.c23-00783

Masaki Higashino, Kiyohiko Sugano

{"title":"Dissolution Profiles of Oral Disintegrating Tablet with Taste Masking Granule Polymer Coating in Biorelevant Bicarbonate Buffer.","authors":"Masaki Higashino, Kiyohiko Sugano","doi":"10.1248/cpb.c23-00783","DOIUrl":"10.1248/cpb.c23-00783","url":null,"abstract":"The current study aimed to explore the impact of buffer species on the dissolution behavior of orally disintegrating tablets (ODT) containing a basic polymer and its influence on bioequivalence (BE) prediction. Fexofenadine hydrochloride ODT formulations were used as the model formulations, Allegra® as the reference formulation, and generic formulations A and B as the test formulations. Allegra®, generic A, and generic B are ODT formulations that contain aminoalkyl methacrylate copolymers E (Eudragit® E, EUD-E), a basic polymer commonly used to mask the bitter taste of drugs. Both generic A and generic B have been known to be bioequivalent to Allegra®. The dissolution tests were conducted using a compendial paddle, with either bicarbonate (10 mM, pH 6.8) or phosphate buffer (25 mM, pH 6.8) as the dissolution media. A floating lid was employed to cover the surface of the bicarbonate buffer to prevent volatilization. Results indicated that in phosphate buffer, the dissolution profiles of Allegra and generic B significantly varied from that of generic A, whereas in the bicarbonate buffer, the dissolution profiles of Allegra, generic A, and generic B were comparable. These findings suggest that the use of bicarbonate buffer may offer a more precise prediction of human bioequivalence compared to phosphate buffer.","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140118918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Late-Stage Derivatization of Oleanolic Acid-Based Anti-HIV-1 Compounds. 齐墩果酸类抗 HIV-1 化合物的后期衍生化。

IF 1.7 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2024-01-01 DOI: 10.1248/cpb.c23-00891

Reon Takeuchi, Junko Fujimoto, Yoshinori Taguchi, Ryuji Ide, Ryuji Kyan, Kohei Sato, Nobuyuki Mase, Masaru Yokoyama, Shigeyoshi Harada, Tetsuo Narumi

{"title":"Late-Stage Derivatization of Oleanolic Acid-Based Anti-HIV-1 Compounds.","authors":"Reon Takeuchi, Junko Fujimoto, Yoshinori Taguchi, Ryuji Ide, Ryuji Kyan, Kohei Sato, Nobuyuki Mase, Masaru Yokoyama, Shigeyoshi Harada, Tetsuo Narumi","doi":"10.1248/cpb.c23-00891","DOIUrl":"10.1248/cpb.c23-00891","url":null,"abstract":"A 12-keto-type oleanolic acid derivative (4) has been identified as a potent anti-human immunodeficiency virus type-1 (HIV-1) compound that demonstrates synergistic effects with several types of HIV-1 neutralizing antibodies. In the present study, we used a common key synthetic intermediate to carry out the late-stage derivatization of an anti-HIV compound based on the chemical structure of a 12-keto-type oleanolic acid derivative. To execute this strategy, we designed a diketo-type oleanolic acid derivative (5) for chemoselective transformation, targeting the carboxy group and the hydroxyl group on the statine unit, as well as the 3-carbonyl group on the oleanolic acid unit, as orthogonal synthetic handles. We carried out four types of chemoselective transformations, leading to identification of the indole-type derivative (16) as a novel potent anti-HIV compound. In addition, further optimization of the β-hydroxyl group on the statine unit provided the R-4-isobutyl γ-amino acid-type derivative (6), which exhibited potent anti-HIV activity comparable to that of 4 but with reduced cytotoxicity.","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140206350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Preparation and in Vitro Characterization of Fatty-Acid Modified Pirarubicin Nanosuspensions Stabilized by Albumin 由白蛋白稳定的脂肪酸修饰的吡柔比星纳米悬浮液的制备与体外表征

IF 1.7 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2024-01-01 DOI: 10.1248/cpb.c23-00701

Takashi Hasegawa, Kenji Tsukigawa, Kindness Commey, Mina Sakuragi, Shuhei Imoto, Kazuaki Taguchi, Koji Nishi, Masaki Otagiri, Keishi Yamasaki

{"title":"Preparation and in Vitro Characterization of Fatty-Acid Modified Pirarubicin Nanosuspensions Stabilized by Albumin","authors":"Takashi Hasegawa, Kenji Tsukigawa, Kindness Commey, Mina Sakuragi, Shuhei Imoto, Kazuaki Taguchi, Koji Nishi, Masaki Otagiri, Keishi Yamasaki","doi":"10.1248/cpb.c23-00701","DOIUrl":"https://doi.org/10.1248/cpb.c23-00701","url":null,"abstract":"Pirarubicin (THP) shows more rapid intracellular uptake, more effective antitumor activity, and less cardiac toxicity, compared to doxorubicin. However, THP is distributed to both tumor and normal tissues indiscriminately. This study aimed to develop a nanosuspension to deliver THP to tumor tissues more efficiently. Fatty-acid-modified THPs (FA-THPs; octanoic acid, dodecanoic acid, palmitic acid-THPs) were synthesized to increase the hydrophobicity of THP. Nanosuspensions of these FA-THPs were then prepared using an antisolvent precipitation technique. Among the FA-THPs, the most efficiently drug-loaded nanosuspension was obtained from palmitic acid-THP (pal-THP) using an aqueous antisolvent containing bovine serum albumin as a stabilizer. The pal-THP nanoparticles in the nanosuspension were confirmed to be of optimal size (100–125 nm) for delivery to tumor tissues using dynamic light scattering and transmission electron microscopy. The pal-THP nanosuspension showed cytotoxicity in colon 26 cells. The nanosuspension was shown to disintegrate in the presence of surfactants such as lecithin, liberating pal-THP, which was converted to free THP in acidic media. It is therefore proposed that pal-THP nanoparticles that reach tumor cells after intravenous administration would exert antitumor effect by liberating pal-THP (i.e., disintegration of nanoparticles by the interaction with cell membrane), followed by the release of free THP in the acidic milieu of tumor cells. These findings indicate that FA-THP nanosuspensions, particularly pal-THP nanosuspension, hold promise as a candidate for cancer treatment. However, further in vivo studies are necessary.\u0000\u0000<img alt=\"\" src=\"https://www.jstage.jst.go.jp/pub/cpb/72/1/72_c23-00701/figure/72_c23-00701.png\"/>\u0000Fullsize Image","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139063648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Identification of Proteolysis Targeting Chimeras (PROTACs) for Lysine Demethylase 5 and Their Neurite Outgrowth-Promoting Activity. 鉴定赖氨酸去甲基化酶 5 的蛋白水解靶向嵌合体 (PROTAC) 及其促进神经元生长的活性

IF 1.5 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2024-01-01 DOI: 10.1248/cpb.c23-00026

Tetsuya Iida, Yukihiro Itoh, Yukari Takahashi, Yuka Miyake, Farzad Zamani, Yasunobu Yamashita, Yuri Takada, Toshiki Akiyama, Jun Ibaraki, Kyoka Okuda, Yuto Tokuda, Tomoka Nishimura, Koto Hidaka, Hiiro Mori, Makoto Oba, Takayoshi Suzuki

{"title":"Identification of Proteolysis Targeting Chimeras (PROTACs) for Lysine Demethylase 5 and Their Neurite Outgrowth-Promoting Activity.","authors":"Tetsuya Iida, Yukihiro Itoh, Yukari Takahashi, Yuka Miyake, Farzad Zamani, Yasunobu Yamashita, Yuri Takada, Toshiki Akiyama, Jun Ibaraki, Kyoka Okuda, Yuto Tokuda, Tomoka Nishimura, Koto Hidaka, Hiiro Mori, Makoto Oba, Takayoshi Suzuki","doi":"10.1248/cpb.c23-00026","DOIUrl":"https://doi.org/10.1248/cpb.c23-00026","url":null,"abstract":"Lysine demethylase 5 (KDM5) proteins are involved in various neurological disorders, including Alzheimer's disease, and KDM5 inhibition is expected to be a therapeutic strategy for these diseases. However, the pharmacological effects of conventional KDM5 inhibitors are insufficient, as they only target the catalytic functionality of KDM5. To identify compounds that exhibit more potent pharmacological activity, we focused on proteolysis targeting chimeras (PROTACs), which degrade target proteins and thus inhibit their entire functionality. We designed and synthesized novel KDM5 PROTAC candidates based on previously identified KDM5 inhibitors. The results of cellular assays revealed that two compounds, 20b and 23b, exhibited significant neurite outgrowth-promoting activity through the degradation of KDM5A in neuroblastoma neuro 2a cells. These results suggest that KDM5 PROTACs are promising drug candidates for the treatment of neurological disorders.","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141466475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Continuous Monitoring of Pseudopolymorphic Transition in Ezetimibe Using T₁ Relaxation with Time-Domain NMR. 利用时域 NMR 的 T1 弛豫连续监测依折麦布的假多晶型转变

IF 1.5 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2024-01-01 DOI: 10.1248/cpb.c24-00215

Takashi Ono, Kotaro Okada, Misaki Kaga, Hidekatsu Eto, Shungo Kumada, Nobuyuki Wakui, Yoshinori Onuki

{"title":"Continuous Monitoring of Pseudopolymorphic Transition in Ezetimibe Using T1 Relaxation with Time-Domain NMR.","authors":"Takashi Ono, Kotaro Okada, Misaki Kaga, Hidekatsu Eto, Shungo Kumada, Nobuyuki Wakui, Yoshinori Onuki","doi":"10.1248/cpb.c24-00215","DOIUrl":"https://doi.org/10.1248/cpb.c24-00215","url":null,"abstract":"The purpose of this study was to continuously monitor the pseudopolymorphic transition from anhydrate to monohydrate by measuring the NMR relaxation using time-domain NMR (TD-NMR). Taking advantage of the simplicity of the low-field NMR instrument configuration, which is an advantage of TD-NMR, the NMR instrument was connected to a humidity controller to monitor the pseudopolymorphic transition. First, ezetimibe (EZT) monohydrate was prepared from its anhydrate using a saturated salt solution method, and T1 relaxation of EZT monohydrate and anhydrate was measured without a humidity controller. The T1 relaxation results confirmed that EZT anhydrate and monohydrate could be distinguished using T1 relaxation measurement. Next, continuous monitoring was conducted by TD-NMR and connected to a humidity controller. Anhydrous EZT was placed in an NMR glass tube and the T1 relaxation measurement was repeated while maintaining the humidity on the side entering the NMR tube at 80% relative humidity. The T1 relaxation became gradually faster from the initial to middle monitoring phases. The final T1 relaxation was then recovered fully and these T1 relaxation times were the same as the T1 relaxation of EZT monohydrate. This study successfully monitored the pseudopolymorphic transition from EZT anhydrate to monohydrate via NMR relaxation.","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141632796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Preparation and Evaluation of Clarithromycin Taste-Masking Dry Suspension Using Hot Melt Extrusion Based on Solid Dispersion Technology. 基于固体分散技术的热熔挤出克拉霉素掩味干混悬剂的制备与评估

IF 1.5 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2024-01-01 DOI: 10.1248/cpb.c24-00206

Tianao Zhang, Min Yu, Yong Fan, Lingyang Wang, Lu Yuan, Yong Sun

{"title":"Preparation and Evaluation of Clarithromycin Taste-Masking Dry Suspension Using Hot Melt Extrusion Based on Solid Dispersion Technology.","authors":"Tianao Zhang, Min Yu, Yong Fan, Lingyang Wang, Lu Yuan, Yong Sun","doi":"10.1248/cpb.c24-00206","DOIUrl":"https://doi.org/10.1248/cpb.c24-00206","url":null,"abstract":"Clarithromycin (CLA) is the preferred drug for treating respiratory infections in pediatric patients, but it has the drawbacks of extreme bitterness and poor water solubility. The purpose of this study was to improve solubility and mask the extreme bitterness of CLA. We use Hot Melt Extrusion (HME) to convert CLA and Eudragit® E100 into Solid Dispersion (SD). Differential scanning calorimetry (DSC) and Powder X-ray diffraction (PXRD) were used to identify the crystalline form of the prepared SDs, which showed that the crystalline CLA was converted to an amorphous form. At the same time, an increase in dissolution rate was observed, which is one of the properties of SD. The results showed that the prepared SD significantly increased the dissolution rate of crystalline CLA. Subsequently, the SD of CLA was prepared into a dry suspension with excellent suspending properties and a taste-masking effect. The bitterness bubble chart and taste radar chart showed that the SD achieved the bitter taste masking of CLA. Principal components analysis (PCA) of the data generated by the electronic tongue showed that the bitter taste of CLA was significantly suppressed using the polymer Eudragit® E100. Subsequently, a dry suspension was prepared from the SD of CLA. In conclusion, this work illustrated the importance of HME for preparing amorphous SD of CLA, which can solve the problems of bitterness-masking and poor solubility. It is also significant for the development of compliant pediatric formulations.","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141632797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Structure Derivatization of IgG-Binding Peptides and Analysis of Their Secondary Structure by Circular Dichroism Spectroscopy. IgG 结合肽的结构衍生及其二级结构的圆二色光谱分析。

IF 1.5 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2024-01-01 DOI: 10.1248/cpb.c24-00430

Kyohei Muguruma, Akane Fukuda, Hayate Shida, Akihiro Taguchi, Kentaro Takayama, Atsuhiko Taniguchi, Yuji Ito, Yoshio Hayashi

{"title":"Structure Derivatization of IgG-Binding Peptides and Analysis of Their Secondary Structure by Circular Dichroism Spectroscopy.","authors":"Kyohei Muguruma, Akane Fukuda, Hayate Shida, Akihiro Taguchi, Kentaro Takayama, Atsuhiko Taniguchi, Yuji Ito, Yoshio Hayashi","doi":"10.1248/cpb.c24-00430","DOIUrl":"10.1248/cpb.c24-00430","url":null,"abstract":"Mid-sized cyclic peptides are a promising modality for modern drug discovery. Their larger interaction area coupled with an appropriate secondary structure is more suitable than small molecules for binding to the target protein. In this study, we conducted a structure derivatization of an immunoglobulin G (IgG)-binding peptide (15-IgBP), a β-hairpin-like cyclic peptide with a twisted β-strand and assessed the effect of the secondary structure on IgG-binding activity using circular dichroism (CD) spectra analysis. As a result, derivatization at the Ala5 and Gly9 positions affected the secondary structure of 15-IgBP, in particular the appearance of a small positive peak in the 220-240 nm region characteristic of 15-IgBP in the CD spectrum. Maintaining this peak at a moderate level may be important for the expression of IgG binding activity. We found the small methyl group at Ala5 to be crucial for retaining the preferred secondary structure; we also found Gly9 could be replaced by D-amino acids. By integrating these findings with previous results of the structure-activity relationship, we obtained four potent affinity peptides for IgG binding (Kd = 4.24-5.85 nM). Furthermore, we found the Gly9 position can be substituted for D-Lys. This is a new potential site for attaching functional units for conjugation with IgG for the preparation of homogeneous antibody-drug conjugates.","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142307186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0