Chemical & pharmaceutical bulletin最新文献

Theoretical Framework for Novel Catalytic Biomolecules Composed of Multiple Peptides 由多肽组成的新型催化生物分子的理论框架

IF 1.7 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2024-09-10 DOI: 10.1248/cpb.c24-00155

Akihiro Ambo, Shiho Ohno, Yoshiki Yamaguchi, Masayuki Seki

{"title":"Theoretical Framework for Novel Catalytic Biomolecules Composed of Multiple Peptides","authors":"Akihiro Ambo, Shiho Ohno, Yoshiki Yamaguchi, Masayuki Seki","doi":"10.1248/cpb.c24-00155","DOIUrl":"https://doi.org/10.1248/cpb.c24-00155","url":null,"abstract":"Protein-based enzymes are among the most efficient catalysts on our planet. A common feature of protein enzymes is that all catalytic amino acids occupy a limited, narrow space and face each other. In this study, we created a theoretical novel biomimetic molecule containing different multiple catalytic peptides. Although single peptides are far less catalytically efficient than protein enzymes, Octopus-arms-mimicking biomolecules containing eight different peptides (Octopuzymes) can efficiently catalyze organic reactions. Since structural information for extant protein enzymes, predicted enzymes based on genome data, and artificially designed enzymes is available for designing Octopuzymes, they could in theory mimic all protein enzyme reactions on our planet. Moreover, besides L-amino acids, peptides can contain D-amino acids, non-natural amino acids, chemically modified amino acids, nucleotides, vitamins, and manmade catalysts, leading to a huge expansion of catalytic space compared with extant protein enzymes. Once a reaction catalyzed by an Octopuzyme is defined, it could be rapidly evolvable via multiple amino acid substitutions on the eight peptides of Octopuzymes.\u0000\u0000<img alt=\"\" src=\"https://www.jstage.jst.go.jp/pub/cpb/72/9/72_c24-00155/figure/72_c24-00155.png\"/>\u0000Fullsize Image","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"8 1","pages":""},"PeriodicalIF":1.7,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142211630","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

Two Preparation Methods for Peptide Thioester Containing Tyr(SO3H) Residue(s) without the Use of Protecting Group for Sulfate Moiety 不使用硫酸基保护基团制备含 Tyr(SO3H) 残基的多肽硫酯的两种方法

IF 1.7 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2024-07-26 DOI: 10.1248/cpb.c24-00212

Yumi Sekigawa, Shinichi Asada, Yurie Ichikawa, Kazuaki Tsubokawa, Shoh Watanabe, Shinobu Honzawa, Kouki Kitagawa

{"title":"Two Preparation Methods for Peptide Thioester Containing Tyr(SO3H) Residue(s) without the Use of Protecting Group for Sulfate Moiety","authors":"Yumi Sekigawa, Shinichi Asada, Yurie Ichikawa, Kazuaki Tsubokawa, Shoh Watanabe, Shinobu Honzawa, Kouki Kitagawa","doi":"10.1248/cpb.c24-00212","DOIUrl":"https://doi.org/10.1248/cpb.c24-00212","url":null,"abstract":"We report two methods for the preparation of peptide thioesters containing Tyr(SO3H) residue(s), without use of a protecting group for the sulfate moiety. The first was based on direct thioesterification using carbodiimide on a fully protected peptide acid, prepared on a 2-chlorotrityl (Clt) resin with fluoren-9-ylmethoxycarbonyl (Fmoc)-based solid-phase peptide synthesis (Fmoc-SPPS). Subsequent deprotection of the protecting groups with trifluoroacetic acid (TFA) (0 °C, 4 h) yielded peptide thioesters containing Tyr(SO3H) residue(s). Peptide thioesters containing one to three Tyr(SO3H) residue(s), prepared by this method, were used as building blocks for the synthesis of the Nα-Fmoc-protected N-terminal part of P-selectin glycoprotein ligand 1 (PSGL-1) (Fmoc-PSGL-1(43–74)) via silver-ion mediated thioester segment condensation. The other method was based on the thioesterification of peptide azide, derived from a peptide hydrazide prepared on a NH2NH-Clt-resin with Fmoc-SPPS. Peptide thioester containing two Tyr(SO3H) residues, prepared via this alternative method, was used as a building block for the one-pot synthesis of the N-terminal extracellular portion of CC-chemokine receptor 5 (CCR5(9–26)) by native chemical ligation (NCL). The two methods for the preparation of peptide thioesters containing Tyr(SO3H) residue(s) described herein are applicable to the synthesis of various types of sulfopeptides.\u0000\u0000<img alt=\"\" src=\"https://www.jstage.jst.go.jp/pub/cpb/72/7/72_c24-00212/figure/72_c24-00212.png\"/>\u0000Fullsize Image","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"55 1","pages":""},"PeriodicalIF":1.7,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141772423","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

Evaluation of STAT3 Inhibition by Cancer Chemopreventive Trichothecenes Derived from Metabolites of Trichothecium roseum 评估从单端孢霉烯代谢物中提取的具有癌症化学预防作用的单端孢霉烯对 STAT3 的抑制作用

IF 1.7 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2024-07-23 DOI: 10.1248/cpb.c24-00300

Mitsuaki Yamashita, Akari Nakanishi, Chiehming Chang, Kosei Tsurushima, Kiyoshige Nakamoto, Akira Iida

{"title":"Evaluation of STAT3 Inhibition by Cancer Chemopreventive Trichothecenes Derived from Metabolites of Trichothecium roseum","authors":"Mitsuaki Yamashita, Akari Nakanishi, Chiehming Chang, Kosei Tsurushima, Kiyoshige Nakamoto, Akira Iida","doi":"10.1248/cpb.c24-00300","DOIUrl":"https://doi.org/10.1248/cpb.c24-00300","url":null,"abstract":"This study evaluated the ability of isolated or semisynthesized trichothecene sesquiterpenes to prevent cancer emergence and proliferation and inhibit signal transducer and activator of transcription-3 (STAT3) phosphorylation through in vitro assays. Trichothecinol A (TTC-A), which bears a hydroxy group at C3, exhibited greater cancer prevention, antiproliferation, and STAT3 phosphorylation inhibition effects than trichothecin (TTC), which lacks a hydroxy group at C3. Furthermore, trichothecinol B (TTC-B), which is a reduced derivative of TTC and has similar cytotoxic effect, showed substantially weaker chemoprotection and STAT3 phosphorylation inhibition effects than TTC. These results clearly indicate that the hydroxy group at C3 and carbonyl group at C8 are crucial for inducing both potent chemoprevention and STAT3 phosphorylation inhibition.\u0000\u0000<img alt=\"\" src=\"https://www.jstage.jst.go.jp/pub/cpb/72/7/72_c24-00300/figure/72_c24-00300.png\"/>\u0000Fullsize Image","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"204 1","pages":""},"PeriodicalIF":1.7,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141753930","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

Total Synthesis of Dinorsesquiterpenoid Oxyphyllin A/Belchinoid A 二异四萜 Oxyphyllin A/Belchinoid A 的全合成

IF 1.7 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2024-07-23 DOI: 10.1248/cpb.c24-00332

Koichiro Ota, Naoya Kashima, Haruhiko Fukaya, Shinnosuke Okazaki, Hiroaki Miyaoka

引用次数: 0

Galangin Promotes Tendon Repair Mediated by Tendon-Derived Stem Cells through Activating the TGF-β1/Smad3 Signaling Pathway 高良姜素通过激活 TGF-β1/Smad3 信号通路促进肌腱衍生干细胞介导的肌腱修复

IF 1.7 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2024-07-13 DOI: 10.1248/cpb.c24-00117

Xiongwei Deng, Qiang Li, Haitao Yuan, Hejun Hu, Shaoyong Fan

{"title":"Galangin Promotes Tendon Repair Mediated by Tendon-Derived Stem Cells through Activating the TGF-β1/Smad3 Signaling Pathway","authors":"Xiongwei Deng, Qiang Li, Haitao Yuan, Hejun Hu, Shaoyong Fan","doi":"10.1248/cpb.c24-00117","DOIUrl":"https://doi.org/10.1248/cpb.c24-00117","url":null,"abstract":"Tendon injury is a prevalent orthopedic disease that currently lacks effective treatment. Galangin (GLN) is a vital flavonoid found abundantly in galangal and is known for its natural activity. This study aimed to investigate the GLN-mediated molecular mechanism of tendon-derived stem cells (TDSCs) in tendon repair. The TDSCs were characterized using alkaline phosphatase staining, alizarin red S staining, oil red O staining, and flow cytometry. The effect of GLN treatment on collagen deposition was evaluated using Sirius red staining and quantitative (q)PCR, while a Western bot was used to assess protein levels and analyze pathways. Results showed that GLN treatment not only increased the collagen deposition but also elevated the mRNA expression and protein levels of multiple tendon markers like collagen type I alpha 1 (COL1A1), decorin (DCN) and tenomodulin (TNMD) in TDSCs. Moreover, GLN was also found to upregulate the protein levels of transforming growth factor β1 (TGF-β1) and p-Smad3 to activate the TGF-β1/Smad3 signaling pathway, while GLN mediated collagen deposition in TDSCs was reversed by LY3200882, a TGF-β receptor inhibitor. The study concluded that GLN-mediated TDSCs enhanced tendon repair by activating the TGF-β1/Smad3 signaling pathway, suggesting a novel therapeutic option in treating tendon repair.\u0000\u0000<img alt=\"\" src=\"https://www.jstage.jst.go.jp/pub/cpb/72/7/72_c24-00117/figure/72_c24-00117.png\"/>\u0000Fullsize Image","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"81 1","pages":""},"PeriodicalIF":1.7,"publicationDate":"2024-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141612989","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

In Vitro and in Silico Study of New Biscoumarin Glycosides from Paramignya trimera against Angiotensin-Converting Enzyme 2 (ACE-2) for Preventing SARS-CoV-2 Infection. 针对血管紧张素转换酶 2（ACE-2）预防 SARS-CoV-2 感染的 Paramignya trimera 新双香豆素苷的体外和硅学研究。

IF 1.5 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2024-06-26 Epub Date: 2024-06-12 DOI: 10.1248/cpb.c23-00844

Nguyen Xuan Ha, Tran Thu Huong, Pham Ngoc Khanh, Nguyen Phi Hung, Vu Thanh Loc, Vu Thi Ha, Dang Thu Quynh, Do Huu Nghi, Pham The Hai, Christopher J Scarlett, Ludger A Wessjohann, Nguyen Manh Cuong

{"title":"In Vitro and in Silico Study of New Biscoumarin Glycosides from Paramignya trimera against Angiotensin-Converting Enzyme 2 (ACE-2) for Preventing SARS-CoV-2 Infection.","authors":"Nguyen Xuan Ha, Tran Thu Huong, Pham Ngoc Khanh, Nguyen Phi Hung, Vu Thanh Loc, Vu Thi Ha, Dang Thu Quynh, Do Huu Nghi, Pham The Hai, Christopher J Scarlett, Ludger A Wessjohann, Nguyen Manh Cuong","doi":"10.1248/cpb.c23-00844","DOIUrl":"10.1248/cpb.c23-00844","url":null,"abstract":"In Vietnam, the stems and roots of the Rutaceous plant Paramignya trimera (Oliv.) Burkill (known locally as \"Xáo tam phân\") are widely used to treat liver diseases such as viral hepatitis and acute and chronic cirrhosis. In an effort to search for Vietnamese natural compounds capable of inhibiting coronavirus based on molecular docking screening, two new dimeric coumarin glycosides, namely cis-paratrimerin B (1) and cis-paratrimerin A (2), and two previously identified coumarins, the trans-isomers paratrimerin B (3) and paratrimerin A (4), were isolated from the roots of P. trimera and tested for their anti-angiotensin-converting enzyme 2 (ACE-2) inhibitory properties in vitro. It was discovered that ACE-2 enzyme was inhibited by cis-paratrimerin B (1), cis-paratrimerin A (2), and trans-paratrimerin B (3), with IC50 values of 28.9, 68, and 77 µM, respectively. Docking simulations revealed that four biscoumarin glycosides had good binding energies (∆G values ranging from -10.6 to -14.7 kcal/mol) and mostly bound to the S1' subsite of the ACE-2 protein. The key interactions of these natural ligands include metal chelation with zinc ions and multiple H-bonds with Ser128, Glu145, His345, Lys363, Thr371, Glu406, and Tyr803. Our findings demonstrated that biscoumarin glycosides from P. trimera roots occur naturally in both cis- and trans-diastereomeric forms. The biscoumarin glycosides Lys363, Thr371, Glu406, and Tyr803. Our findings demonstrated that biscoumarin glycosides from P. trimera roots hold potential for further studies as natural ACE-2 inhibitors for preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":" ","pages":"574-583"},"PeriodicalIF":1.5,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141310091","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

Understanding the Manufacturing Process of Lipid Nanoparticles for mRNA Delivery Using Machine Learning 利用机器学习了解用于 mRNA 运送的脂质纳米粒子的制造过程

IF 1.7 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2024-06-05 DOI: 10.1248/cpb.c24-00089

Shinya Sato, Syusuke Sano, Hiroki Muto, Kenji Kubara, Keita Kondo, Takayuki Miyazaki, Yuta Suzuki, Yoshifumi Uemoto, Koji Ukai

{"title":"Understanding the Manufacturing Process of Lipid Nanoparticles for mRNA Delivery Using Machine Learning","authors":"Shinya Sato, Syusuke Sano, Hiroki Muto, Kenji Kubara, Keita Kondo, Takayuki Miyazaki, Yuta Suzuki, Yoshifumi Uemoto, Koji Ukai","doi":"10.1248/cpb.c24-00089","DOIUrl":"https://doi.org/10.1248/cpb.c24-00089","url":null,"abstract":"Lipid nanoparticles (LNPs), used for mRNA vaccines against severe acute respiratory syndrome coronavirus 2, protect mRNA and deliver it into cells, making them an essential delivery technology for RNA medicine. The LNPs manufacturing process consists of two steps, the upstream process of preparing LNPs and the downstream process of removing ethyl alcohol (EtOH) and exchanging buffers. Generally, a microfluidic device is used in the upstream process, and a dialysis membrane is used in the downstream process. However, there are many parameters in the upstream and downstream processes, and it is difficult to determine the effects of variations in the manufacturing parameters on the quality of the LNPs and establish a manufacturing process to obtain high-quality LNPs. This study focused on manufacturing mRNA-LNPs using a microfluidic device. Extreme gradient boosting (XGBoost), which is a machine learning technique, identified EtOH concentration (flow rate ratio), buffer pH, and total flow rate as the process parameters that significantly affected the particle size and encapsulation efficiency. Based on these results, we derived the manufacturing conditions for different particle sizes (approximately 80 and 200 nm) of LNPs using Bayesian optimization. In addition, the particle size of the LNPs significantly affected the protein expression level of mRNA in cells. The findings of this study are expected to provide useful information that will enable the rapid and efficient development of mRNA-LNPs manufacturing processes using microfluidic devices.\u0000\u0000<img alt=\"\" src=\"https://www.jstage.jst.go.jp/pub/cpb/72/6/72_c24-00089/figure/72_c24-00089.png\"/>\u0000Fullsize Image","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"66 1","pages":""},"PeriodicalIF":1.7,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141253170","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

Theoretical Study of Natural Product Biosynthesis Using Computational Chemistry 利用计算化学的天然产物生物合成理论研究

IF 1.7 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2024-06-01 DOI: 10.1248/cpb.c24-00082

Hajime Sato

引用次数: 0

Viscosity-Induced Emission of 5-(Diarylmethylene)imidazolone with Extended Conjugation via Attachment of N-Methylpyrrole at the 2-Position 通过在 2-位连接 N-甲基吡咯扩展共轭的 5-(二亚甲基)咪唑啉酮的粘度诱导发射

IF 1.7 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2024-05-31 DOI: 10.1248/cpb.c24-00143

Masahiro Ikejiri, Aki Yoshimizu, Fumika Shiota, Ai Nagayama, Aki Fujisaka, Yuichi Kuboki, Kazuyuki Miyashita

引用次数: 0

Intracellular Delivery of Plasmid DNA Using Amphipathic Helical Cell-Penetrating Peptides Containing Dipropylglycine 利用含有二丙基甘氨酸的两性螺旋细胞穿透肽进行质粒 DNA 的细胞内递送

IF 1.7 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2024-05-29 DOI: 10.1248/cpb.c24-00221

Motoki Naka, Tomohiro Umeno, Mika Shibuya, Yuto Yamaberi, Atsushi Ueda, Masakazu Tanaka, Hiroyasu Takemoto, Makoto Oba

{"title":"Intracellular Delivery of Plasmid DNA Using Amphipathic Helical Cell-Penetrating Peptides Containing Dipropylglycine","authors":"Motoki Naka, Tomohiro Umeno, Mika Shibuya, Yuto Yamaberi, Atsushi Ueda, Masakazu Tanaka, Hiroyasu Takemoto, Makoto Oba","doi":"10.1248/cpb.c24-00221","DOIUrl":"https://doi.org/10.1248/cpb.c24-00221","url":null,"abstract":"Cell-penetrating peptides (CPPs) serve as potent vehicles for delivering membrane-impermeable compounds, including nucleic acids, into cells. In a previous study, we reported the successful intracellular delivery of small interfering RNAs (siRNAs) with negligible cytotoxicity using a peptide containing an unnatural amino acid (dipropylglycine). In the present study, we employed the same seven peptides as the previous study to evaluate their efficacy in delivering plasmid DNA (pDNA) intracellularly. Although pDNA and siRNA are nucleic acids, they differ in size and biological function, which may influence the optimal peptide sequences for their delivery. Herein, three peptides demonstrated effective pDNA transfection abilities. Notably, only one of the three peptides previously exhibited efficient gene-silencing effect with siRNA. These findings validate our hypothesis and offer insights for the personalized design of CPPs for the delivery of pDNA and siRNA.\u0000\u0000<img alt=\"\" src=\"https://www.jstage.jst.go.jp/pub/cpb/72/5/72_c24-00221/figure/72_c24-00221.png\"/>\u0000Fullsize Image","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"223 1","pages":""},"PeriodicalIF":1.7,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141165656","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