首页 > 最新文献

Exploration of drug science最新文献

英文 中文
In silico study about β-amyloid’s role in Alzheimer’s disease and glaucoma and prediction of its interactions with glaucoma related proteins β-淀粉样蛋白在阿尔茨海默病和青光眼中的作用及其与青光眼相关蛋白相互作用的预测
Pub Date : 2023-08-29 DOI: 10.37349/eds.2023.00018
N. Maurya
Aim: The significance of β-amyloid protein as a key player in neuro-degenerative disorders viz. Alzheimer’s disease (AD), Parkinson’s disease (PD) has been extensively researched and reported. Glaucoma being another prominent form of neuro-degeneration involving the loss of retinal ganglion cells (RGCs) and human trabecular meshwork (HTM) cells, is also found to be similar to AD in many aspects, but its relation with β-amyloid has not been studied too far up to understanding its causation and pathogenesis where β-amyloid is expected to play important role. This study is an attempt to evaluate the chances of β-amyloid’s role in pathogenesis of retinal neurodegenerative disorder called glaucoma, in silico.Methods: The study involved determination of feasibility of interaction between β-amyloid and well known glaucoma related proteins namely, myocilin and optineurin. The computational tool called Hex 8.0.0 has been used in this work.Results: The docking score for β-amyloid and myocilin was found to be –724.1 kJ mol–1 while that for β-amyloid and wild-type optineurin pair was found to be –296.9 kJ mol–1 and that for β-amyloid and mutated optineurin was –607.1 kJ mol–1.Conclusions: Interaction of β-amyloid with myocilin and optineurin in both forms (wild-type and mutated) is quite energetically favorable. The binding between β-amyloid and mutated optineurin is higher in comparison to that between β-amyloid and wild-type optineurin. Thus, functional significance of β-amyloid in glaucoma pathogenesis is fairly possible which should be studied and proved through in vitro and in vivo studies.
目的:β-淀粉样蛋白在神经退行性疾病如阿尔茨海默病(AD)、帕金森病(PD)中的重要作用已被广泛研究和报道。青光眼是另一种突出的神经变性形式,涉及视网膜神经节细胞(RGCs)和人小梁网(HTM)细胞的损失,也被发现在许多方面与AD相似,但其与β-淀粉样蛋白的关系尚未深入研究,尚未了解其病因和发病机制,其中β-淀粉样蛋白有望发挥重要作用。本研究旨在评估β-淀粉样蛋白在青光眼视网膜神经退行性疾病发病机制中的作用。方法:研究β-淀粉样蛋白与青光眼相关蛋白,即心肌蛋白和视神经蛋白相互作用的可行性。在这项工作中使用了名为Hex 8.0.0的计算工具。结果:β-淀粉样蛋白与心肌蛋白的对接评分为-724.1 kJ mol-1, β-淀粉样蛋白与野生型优神经蛋白的对接评分为-296.9 kJ mol-1, β-淀粉样蛋白与突变优神经蛋白的对接评分为-607.1 kJ mol-1。结论:β-淀粉样蛋白与两种形式(野生型和突变型)的心肌蛋白和优神经蛋白相互作用在能量上是非常有利的。β-淀粉样蛋白与突变的优神经蛋白的结合比β-淀粉样蛋白与野生型优神经蛋白的结合更高。因此,β-淀粉样蛋白在青光眼发病机制中的功能意义是很有可能的,需要通过体外和体内研究来研究和证实。
{"title":"In silico study about β-amyloid’s role in Alzheimer’s disease and glaucoma and prediction of its interactions with glaucoma related proteins","authors":"N. Maurya","doi":"10.37349/eds.2023.00018","DOIUrl":"https://doi.org/10.37349/eds.2023.00018","url":null,"abstract":"Aim: The significance of β-amyloid protein as a key player in neuro-degenerative disorders viz. Alzheimer’s disease (AD), Parkinson’s disease (PD) has been extensively researched and reported. Glaucoma being another prominent form of neuro-degeneration involving the loss of retinal ganglion cells (RGCs) and human trabecular meshwork (HTM) cells, is also found to be similar to AD in many aspects, but its relation with β-amyloid has not been studied too far up to understanding its causation and pathogenesis where β-amyloid is expected to play important role. This study is an attempt to evaluate the chances of β-amyloid’s role in pathogenesis of retinal neurodegenerative disorder called glaucoma, in silico.\u0000Methods: The study involved determination of feasibility of interaction between β-amyloid and well known glaucoma related proteins namely, myocilin and optineurin. The computational tool called Hex 8.0.0 has been used in this work.\u0000Results: The docking score for β-amyloid and myocilin was found to be –724.1 kJ mol–1 while that for β-amyloid and wild-type optineurin pair was found to be –296.9 kJ mol–1 and that for β-amyloid and mutated optineurin was –607.1 kJ mol–1.\u0000Conclusions: Interaction of β-amyloid with myocilin and optineurin in both forms (wild-type and mutated) is quite energetically favorable. The binding between β-amyloid and mutated optineurin is higher in comparison to that between β-amyloid and wild-type optineurin. Thus, functional significance of β-amyloid in glaucoma pathogenesis is fairly possible which should be studied and proved through in vitro and in vivo studies.","PeriodicalId":72998,"journal":{"name":"Exploration of drug science","volume":"71 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83927595","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}
引用次数: 0
Natural compounds from medicinal plants against COVID-19 抗COVID-19的药用植物天然化合物
Pub Date : 2023-08-28 DOI: 10.37349/eds.2023.00017
A. Kolodnitsky, N. Ionov, I. Gravel, V. Poroikov
The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), known to cause the coronavirus disease 2019 (COVID-19), was declared a pandemic in early 2020. During the past time, several infections control methods have been developed. Nevertheless, all of them have certain limitations: uncertainty in duration, limited efficacy of vaccines, and lack of effective drugs for COVID-19 treatment. So, the issue of creating drugs for symptomatic and etiotropic therapy is still relevant. This review summarizes the current knowledge of using natural compounds as anti-SARS-CoV-2 agents by analysing the results of in vitro studies and completed clinical trials (CTs). Also, this work highlighted the most active molecules and discussed the possibility of using some compounds in clinical practice.
已知导致2019冠状病毒病(COVID-19)的严重急性呼吸综合征冠状病毒-2 (SARS-CoV-2)于2020年初被宣布为大流行。在过去的一段时间里,已经开发了几种感染控制方法。然而,它们都有一定的局限性:持续时间的不确定性、疫苗的效力有限、缺乏有效的COVID-19治疗药物。因此,为对症和致病因治疗创造药物的问题仍然是相关的。本文通过分析体外研究和已完成的临床试验(CTs)的结果,总结了目前使用天然化合物作为抗sars - cov -2药物的知识。此外,本工作突出了最具活性的分子,并讨论了在临床实践中使用某些化合物的可能性。
{"title":"Natural compounds from medicinal plants against COVID-19","authors":"A. Kolodnitsky, N. Ionov, I. Gravel, V. Poroikov","doi":"10.37349/eds.2023.00017","DOIUrl":"https://doi.org/10.37349/eds.2023.00017","url":null,"abstract":"The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), known to cause the coronavirus disease 2019 (COVID-19), was declared a pandemic in early 2020. During the past time, several infections control methods have been developed. Nevertheless, all of them have certain limitations: uncertainty in duration, limited efficacy of vaccines, and lack of effective drugs for COVID-19 treatment. So, the issue of creating drugs for symptomatic and etiotropic therapy is still relevant. This review summarizes the current knowledge of using natural compounds as anti-SARS-CoV-2 agents by analysing the results of in vitro studies and completed clinical trials (CTs). Also, this work highlighted the most active molecules and discussed the possibility of using some compounds in clinical practice.","PeriodicalId":72998,"journal":{"name":"Exploration of drug science","volume":"20 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88624414","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}
引用次数: 0
Iron depletion in “metabolic fatty liver syndromes”: a strong biological rationale with disappointing liver outcomes “代谢性脂肪肝综合征”中的铁缺乏:一个令人失望的肝脏结局的强有力的生物学原理
Pub Date : 2023-08-28 DOI: 10.37349/eds.2023.00016
A. Lonardo
Nonalcoholic fatty liver disease (NAFLD), its more rapidly progressive steatohepatitic variant [nonalcoholic steatohepatitis, (NASH)], and the recently defined metabolic dysfunction-associated fatty liver disease (MAFLD) may be collectively alluded to as “metabolic fatty liver syndromes” (MFLS). MFLS is a common clinical complaint for which no licensed drug treatment is available and a public health issue posing a heaven burden on healthcare systems. Iron plays a key role in many of the key pathogenic steps concurring in the development and progression of MFLS, notably including genetics, intestinal dysbiosis, adipositis, insulin resistance (IR), metaflammation, oxidative stress and ferroptosis, endoplasmic reticulum (ER) stress, and hepatic fibrosis (FIB). This notion raises the logical expectation that iron depletion, which can easily be implemented with venesection, might improve several aspects of MFLS. However, few published studies have globally failed to support these expectations. In conclusion, venesection in MFLS exhibits a strong biological rationale and possible metabolic benefits. However, confronted with failures in hepato-histological outcomes, data call for additional studies aimed to reconcile these inconsistencies.
非酒精性脂肪性肝病(NAFLD),其进展更为迅速的脂肪性肝炎变型[非酒精性脂肪性肝炎(NASH)],以及最近定义的代谢功能障碍相关脂肪性肝病(MAFLD)可统称为“代谢性脂肪肝综合征”(MFLS)。MFLS是一种常见的临床主诉,没有许可的药物治疗,是一个公共卫生问题,对卫生保健系统构成沉重负担。铁在MFLS发生和发展的许多关键致病步骤中起着关键作用,特别是遗传学、肠道生态失调、脂肪炎、胰岛素抵抗(IR)、炎症、氧化应激和铁凋亡、内质网(ER)应激和肝纤维化(FIB)。这个概念提出了一个合乎逻辑的期望,即铁的消耗,可以很容易地通过静脉切断实现,可能会改善MFLS的几个方面。然而,在全球范围内,很少有已发表的研究未能支持这些期望。总之,MFLS的静脉切除具有很强的生物学原理和可能的代谢益处。然而,面对肝脏组织学结果的失败,数据要求进一步的研究旨在调和这些不一致性。
{"title":"Iron depletion in “metabolic fatty liver syndromes”: a strong biological rationale with disappointing liver outcomes","authors":"A. Lonardo","doi":"10.37349/eds.2023.00016","DOIUrl":"https://doi.org/10.37349/eds.2023.00016","url":null,"abstract":"Nonalcoholic fatty liver disease (NAFLD), its more rapidly progressive steatohepatitic variant [nonalcoholic steatohepatitis, (NASH)], and the recently defined metabolic dysfunction-associated fatty liver disease (MAFLD) may be collectively alluded to as “metabolic fatty liver syndromes” (MFLS). MFLS is a common clinical complaint for which no licensed drug treatment is available and a public health issue posing a heaven burden on healthcare systems. Iron plays a key role in many of the key pathogenic steps concurring in the development and progression of MFLS, notably including genetics, intestinal dysbiosis, adipositis, insulin resistance (IR), metaflammation, oxidative stress and ferroptosis, endoplasmic reticulum (ER) stress, and hepatic fibrosis (FIB). This notion raises the logical expectation that iron depletion, which can easily be implemented with venesection, might improve several aspects of MFLS. However, few published studies have globally failed to support these expectations. In conclusion, venesection in MFLS exhibits a strong biological rationale and possible metabolic benefits. However, confronted with failures in hepato-histological outcomes, data call for additional studies aimed to reconcile these inconsistencies.","PeriodicalId":72998,"journal":{"name":"Exploration of drug science","volume":"24 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76209156","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}
引用次数: 0
Approved antibacterial drugs in the last 10 years: from the bench to the clinic 过去10年被批准的抗菌药物:从实验室到临床
Pub Date : 2023-06-30 DOI: 10.37349/eds.2023.00013
M. García-Castro, F. Sarabia, Amelia Díaz-Morilla, J. López-Romero
Bacterial infections constitute one of the major cases of primary medical incidences worldwide. Historically, the fight against bacterial infections in humans has been an ongoing battle, due to the ability of bacteria to adapt and to survive. Indeed, bacteria have developed various mechanisms of resistance against several therapeutic agents. Consequently, the scientific community is always interested in search of new therapeutic agents, which are able to efficiently kill resistant-bacterial strains. This article covers the most recent antibacterial molecules approved by the Food and Drugs Administration (FDA) and European Medicines Agency (EMA) from 2012 to 2022 and intends to focus on synthetic derivatives to give a pedagogical view, with the goal of highlighting the importance of organic synthesis to obtain greater efficacy. A focus will be made on studies describing the structure and activity of the organic molecules and their interactions with their respective biological targets.
细菌感染是世界范围内主要的初级医疗事件之一。从历史上看,人类与细菌感染的斗争一直是一场持续的战斗,因为细菌有适应和生存的能力。事实上,细菌已经发展出对几种治疗药物的各种抵抗机制。因此,科学界总是对寻找能够有效杀死耐药菌株的新治疗剂感兴趣。本文涵盖了2012年至2022年美国食品和药物管理局(FDA)和欧洲药品管理局(EMA)批准的最新抗菌分子,并打算将重点放在合成衍生物上,以提供教学观点,目的是强调有机合成的重要性,以获得更大的功效。重点将放在描述有机分子的结构和活性及其与各自生物靶点的相互作用的研究上。
{"title":"Approved antibacterial drugs in the last 10 years: from the bench to the clinic","authors":"M. García-Castro, F. Sarabia, Amelia Díaz-Morilla, J. López-Romero","doi":"10.37349/eds.2023.00013","DOIUrl":"https://doi.org/10.37349/eds.2023.00013","url":null,"abstract":"Bacterial infections constitute one of the major cases of primary medical incidences worldwide. Historically, the fight against bacterial infections in humans has been an ongoing battle, due to the ability of bacteria to adapt and to survive. Indeed, bacteria have developed various mechanisms of resistance against several therapeutic agents. Consequently, the scientific community is always interested in search of new therapeutic agents, which are able to efficiently kill resistant-bacterial strains. This article covers the most recent antibacterial molecules approved by the Food and Drugs Administration (FDA) and European Medicines Agency (EMA) from 2012 to 2022 and intends to focus on synthetic derivatives to give a pedagogical view, with the goal of highlighting the importance of organic synthesis to obtain greater efficacy. A focus will be made on studies describing the structure and activity of the organic molecules and their interactions with their respective biological targets.","PeriodicalId":72998,"journal":{"name":"Exploration of drug science","volume":"18 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81838944","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}
引用次数: 0
A dextrorotatory residues-incorporated bioactive dodecapeptide against enterohemorrhagic Escherichia coli 抗肠出血性大肠杆菌的右旋残渣结合生物活性十二肽
Pub Date : 2023-06-30 DOI: 10.37349/eds.2023.00014
Ping Zeng, Xuemei Yang, K. Wong, Sheng Chen, Kin-Fai Chan, S. Leung, Lanhua Yi
Aim: This study aims to report an engineered peptide zp39 with favorable bioactivity against enterohemorrhagic Escherichia coli (E. coli, EHEC). Its antibacterial mechanisms and application in a real food system are assessed.Methods: Spatial conformation of synthetic peptide zp39 (GIIAGIIiKIKk-NH2, lowercase letters indicate dextrorotatory amino acids) was predicted by PEPstrMOD and its secondary structure was further determined by circular dichroism (CD) spectroscopy. Then, standard E. coli O157:H7 strain ATCC 43888 was used to evaluate the bioactivity of zp39. A double dilution method was applied to investigate its efficacy in normal broth medium, serum, and highly saline conditions. Its effects on cell membrane permeability and potential were measured by fluorescent assays. Thereafter, morphological changes of E. coli O157:H7 cells were monitored by electron microscopy technologies. Finally, the potential application of zp39 in controlling EHEC in food was tested with spinach juice and the Galleria mellonella larvae model was employed to assess the in vivo efficacy.Results: Peptide zp39 presented an amphiphilic helical structure. It effectively inhibited the growth of E. coli O157:H7 at a concentration of 4 μmol/L in a bactericidal mode. Mechanistic studies revealed that it affected membrane permeability and potential in a dose-dependent manner. Moreover, zp39 maintained satisfactory bioactivity against E. coli O157:H7 even in the presence of 70% serum or 1,000 μmol/L chloride salts. In spinach juice application, > 90% E. coli O157:H7 cells were killed within 2 h after exposure to 64 μmol/L zp39. In vivo study proved that treatment with 64 μmol/L zp39 could effectively boost the survival ratio of infected larvae by 50%.Conclusions: This study depicts a synthetic dodecapeptide that shows the potential application in controlling EHEC. This molecule may be developed into a highly effective antimicrobial agent applied to prevent food contamination and associated infections.
目的:本研究旨在报道一种具有良好抗肠出血性大肠杆菌生物活性的工程肽zp39。评价了其抗菌机理及其在实际食品体系中的应用。方法:利用PEPstrMOD预测合成肽zp39 (GIIAGIIiKIKk-NH2,小写字母表示右旋氨基酸)的空间构象,并利用圆二色性(CD)光谱进一步测定其二级结构。然后用标准菌株ATCC 43888评价zp39的生物活性。采用双倍稀释法考察其在正常肉汤培养基、血清和高盐条件下的疗效。用荧光法测定其对细胞膜通透性和电位的影响。随后,用电镜技术监测大肠杆菌O157:H7细胞形态学变化。最后,利用菠菜汁检测zp39在控制食品中肠出血性大肠杆菌中的应用潜力,并采用大mellonera幼虫模型评价其体内效果。结果:肽zp39呈两亲性螺旋结构。在4 μmol/L的浓度下,能有效抑制大肠杆菌O157:H7的生长。机制研究表明,它以剂量依赖的方式影响膜透性和电位。zp39在70%血清或1000 μmol/L氯盐的存在下,对大肠杆菌O157:H7仍保持良好的生物活性。在菠菜汁处理中,64 μmol/L zp39处理后2 h内杀灭大肠杆菌O157:H7细胞的比例大于90%。体内实验证明,64 μmol/L zp39处理可有效提高感染幼虫的存活率50%。结论:本研究描述了一种合成的十二肽,在控制肠出血性大肠杆菌方面具有潜在的应用前景。该分子可发展成为一种高效的抗菌剂,用于预防食品污染和相关感染。
{"title":"A dextrorotatory residues-incorporated bioactive dodecapeptide against enterohemorrhagic Escherichia coli","authors":"Ping Zeng, Xuemei Yang, K. Wong, Sheng Chen, Kin-Fai Chan, S. Leung, Lanhua Yi","doi":"10.37349/eds.2023.00014","DOIUrl":"https://doi.org/10.37349/eds.2023.00014","url":null,"abstract":"Aim: This study aims to report an engineered peptide zp39 with favorable bioactivity against enterohemorrhagic Escherichia coli (E. coli, EHEC). Its antibacterial mechanisms and application in a real food system are assessed.\u0000Methods: Spatial conformation of synthetic peptide zp39 (GIIAGIIiKIKk-NH2, lowercase letters indicate dextrorotatory amino acids) was predicted by PEPstrMOD and its secondary structure was further determined by circular dichroism (CD) spectroscopy. Then, standard E. coli O157:H7 strain ATCC 43888 was used to evaluate the bioactivity of zp39. A double dilution method was applied to investigate its efficacy in normal broth medium, serum, and highly saline conditions. Its effects on cell membrane permeability and potential were measured by fluorescent assays. Thereafter, morphological changes of E. coli O157:H7 cells were monitored by electron microscopy technologies. Finally, the potential application of zp39 in controlling EHEC in food was tested with spinach juice and the Galleria mellonella larvae model was employed to assess the in vivo efficacy.\u0000Results: Peptide zp39 presented an amphiphilic helical structure. It effectively inhibited the growth of E. coli O157:H7 at a concentration of 4 μmol/L in a bactericidal mode. Mechanistic studies revealed that it affected membrane permeability and potential in a dose-dependent manner. Moreover, zp39 maintained satisfactory bioactivity against E. coli O157:H7 even in the presence of 70% serum or 1,000 μmol/L chloride salts. In spinach juice application, > 90% E. coli O157:H7 cells were killed within 2 h after exposure to 64 μmol/L zp39. In vivo study proved that treatment with 64 μmol/L zp39 could effectively boost the survival ratio of infected larvae by 50%.\u0000Conclusions: This study depicts a synthetic dodecapeptide that shows the potential application in controlling EHEC. This molecule may be developed into a highly effective antimicrobial agent applied to prevent food contamination and associated infections.","PeriodicalId":72998,"journal":{"name":"Exploration of drug science","volume":"17 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83172877","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}
引用次数: 0
Identification of an inter-cysteine loop potentially involved in the activity of Opisthorchis viverrini-granulin-1 半胱氨酸间环的鉴定可能参与了蛇胸菌颗粒蛋白-1的活性
Pub Date : 2023-06-30 DOI: 10.37349/eds.2023.00012
R. Takjoo, David T. Wilson, P. Bansal, A. Loukas, M. Smout, N. Daly
Aim: Identification of small bioactive regions in proteins and peptides can be useful information in drug design studies. The current study has shown that an inter-cysteine loop of the N-terminal domain of Opisthorchis viverrini granulin-1 (Ov-GRN-1), a granulin protein from the flatworm liver fluke Opisthorchis viverrini which has potent wound healing properties, maintains the bioactivity of the full-length protein.Methods: Peptides corresponding to the three inter-cysteine loops of the N-terminal domain were produced using synthetic chemistry, and their structures and bioactivities were analyzed using nuclear magnetic resonance (NMR) spectroscopy and cell proliferation assays, respectively.Results: As expected for such small peptides, NMR analysis indicated that the peptides were poorly structured in solution. However, a seven-residue peptide corresponding to loop 2 (GRN-L2) promoted cell proliferation, in contrast to the other fragments.Conclusions: The results from the current study suggest that GRN-L2 might be responsible, in part, for the bioactivity of Ov-GRN-1, and might be a useful lead molecule for subsequent wound healing studies.
目的:鉴定蛋白质和多肽中的小生物活性区域可以为药物设计研究提供有用的信息。目前的研究表明,来自扁平虫肝吸虫的颗粒蛋白Opisthorchis viverrini granulin-1 (Ov-GRN-1)的n端结构域的半胱氨酸间环维持了全长蛋白的生物活性,该蛋白具有强大的伤口愈合特性。方法:采用合成化学方法制备与n端结构域3个半胱氨酸间环对应的多肽,分别采用核磁共振(NMR)和细胞增殖实验对其结构和生物活性进行分析。结果:正如预期的那样,核磁共振分析表明这种小肽在溶液中结构不良。然而,与其他片段相比,环2对应的七残基肽(GRN-L2)促进了细胞增殖。结论:目前的研究结果表明,GRN-L2可能是Ov-GRN-1生物活性的部分原因,可能是后续伤口愈合研究中有用的先导分子。
{"title":"Identification of an inter-cysteine loop potentially involved in the activity of Opisthorchis viverrini-granulin-1","authors":"R. Takjoo, David T. Wilson, P. Bansal, A. Loukas, M. Smout, N. Daly","doi":"10.37349/eds.2023.00012","DOIUrl":"https://doi.org/10.37349/eds.2023.00012","url":null,"abstract":"Aim: Identification of small bioactive regions in proteins and peptides can be useful information in drug design studies. The current study has shown that an inter-cysteine loop of the N-terminal domain of Opisthorchis viverrini granulin-1 (Ov-GRN-1), a granulin protein from the flatworm liver fluke Opisthorchis viverrini which has potent wound healing properties, maintains the bioactivity of the full-length protein.\u0000Methods: Peptides corresponding to the three inter-cysteine loops of the N-terminal domain were produced using synthetic chemistry, and their structures and bioactivities were analyzed using nuclear magnetic resonance (NMR) spectroscopy and cell proliferation assays, respectively.\u0000Results: As expected for such small peptides, NMR analysis indicated that the peptides were poorly structured in solution. However, a seven-residue peptide corresponding to loop 2 (GRN-L2) promoted cell proliferation, in contrast to the other fragments.\u0000Conclusions: The results from the current study suggest that GRN-L2 might be responsible, in part, for the bioactivity of Ov-GRN-1, and might be a useful lead molecule for subsequent wound healing studies.","PeriodicalId":72998,"journal":{"name":"Exploration of drug science","volume":"18 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80991920","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}
引用次数: 0
Nature-inspired and medicinally relevant short peptides 自然启发和医学相关的短肽
Pub Date : 2023-06-27 DOI: 10.37349/eds.2023.00011
M. G. Ciulla, M. Civera, S. Sattin, Kamal Kumar
Peptides constitute an important component of Nature’s pharmacy and they play a significant role in several signaling pathways acting as natural biological messengers. While nature has mastered the cycle of creation, application, and destruction of large and short peptides to the benefit of the host organism, organic and medicinal chemists have in their capacity and small steps, made big developments in the field of peptide synthesis as well as in developing them as therapeutics. In comparison to their big counterparts, i.e. proteins, short peptides encompass several advantages, from the ease of synthesis to their physico-chemical properties. However, the real challenge for in vivo application of therapeutic peptides is to overcome their low plasma availability and their fast enzymatic degradation. This review briefly covers the relevant areas of medicinally important short peptides and the recent developments made to turn these peptides into therapeutics. Also presented in this article are important efforts and strategies used to overcome some of the inherent limitations of peptidic molecules and thereby facilitate their progression in the clinical phases towards approved drugs.
多肽是自然药物的重要组成部分,作为天然生物信使,在多种信号通路中发挥着重要作用。虽然大自然已经掌握了大肽和短肽的创造、应用和破坏的循环,以造福宿主生物,但有机和药物化学家凭借他们的能力和小步,在肽合成领域取得了重大进展,并将其开发为治疗方法。与它们的大对应物,即蛋白质相比,短肽具有几个优点,从易于合成到其物理化学性质。然而,治疗肽在体内应用的真正挑战是克服其低血浆利用率和快速酶降解。本文简要介绍了具有重要医学意义的短肽的相关领域以及将这些短肽转化为治疗药物的最新进展。本文还介绍了用于克服肽分子固有局限性的重要努力和策略,从而促进其在临床阶段向批准药物的进展。
{"title":"Nature-inspired and medicinally relevant short peptides","authors":"M. G. Ciulla, M. Civera, S. Sattin, Kamal Kumar","doi":"10.37349/eds.2023.00011","DOIUrl":"https://doi.org/10.37349/eds.2023.00011","url":null,"abstract":"Peptides constitute an important component of Nature’s pharmacy and they play a significant role in several signaling pathways acting as natural biological messengers. While nature has mastered the cycle of creation, application, and destruction of large and short peptides to the benefit of the host organism, organic and medicinal chemists have in their capacity and small steps, made big developments in the field of peptide synthesis as well as in developing them as therapeutics. In comparison to their big counterparts, i.e. proteins, short peptides encompass several advantages, from the ease of synthesis to their physico-chemical properties. However, the real challenge for in vivo application of therapeutic peptides is to overcome their low plasma availability and their fast enzymatic degradation. This review briefly covers the relevant areas of medicinally important short peptides and the recent developments made to turn these peptides into therapeutics. Also presented in this article are important efforts and strategies used to overcome some of the inherent limitations of peptidic molecules and thereby facilitate their progression in the clinical phases towards approved drugs.","PeriodicalId":72998,"journal":{"name":"Exploration of drug science","volume":"220 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88025246","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}
引用次数: 1
Heterogeneous graph convolutional neural network for protein-ligand scoring 蛋白质配体评分的异构图卷积神经网络
Pub Date : 2023-04-30 DOI: 10.37349/eds.2023.00010
Kevin Crampon, Alexis Giorkallos, X. Vigouroux, S. Baud, L. Steffenel
Aim: Drug discovery is a long process, often taking decades of research endeavors. It is still an active area of research in both academic and industrial sectors with efforts on reducing time and cost. Computational simulations like molecular docking enable fast exploration of large databases of compounds and extract the most promising molecule candidates for further in vitro and in vivo tests. Structure-based molecular docking is a complex process mixing both surface exploration and energy estimation to find the minimal free energy of binding corresponding to the best interaction location.Methods: Hereafter, heterogeneous graph score (HGScore), a new scoring function is proposed and is developed in the context of a protein-small compound-complex. Each complex is represented by a heterogeneous graph allowing to separate edges according to their class (inter- or intra-molecular). Then a heterogeneous graph convolutional network (HGCN) is used allowing the discrimination of the information according to the edge crossed. In the end, the model produces the affinity score of the complex.Results: HGScore has been tested on the comparative assessment of scoring functions (CASF) 2013 and 2016 benchmarks for scoring, ranking, and docking powers. It has achieved good performances by outperforming classical methods and being among the best artificial intelligence (AI) methods.Conclusions: Thus, HGScore brings a new way to represent protein-ligand interactions. Using a representation that involves classical graph neural networks (GNNs) and splitting the learning process regarding the edge type makes the proposed model to be the best adapted for future transfer learning on other (protein-DNA, protein-sugar, protein-protein, etc.) biological complexes.
目的:药物发现是一个漫长的过程,通常需要几十年的研究努力。它仍然是一个活跃的研究领域,在学术界和工业界的努力,以减少时间和成本。像分子对接这样的计算模拟可以快速探索大型化合物数据库,并提取最有希望的候选分子,用于进一步的体外和体内测试。基于结构的分子对接是寻找最佳相互作用位置对应的最小结合自由能的复杂过程。方法:本文提出了一种新的评分函数HGScore (heterogeneous graph score),并在蛋白质-小化合物-复合物的背景下进行了开发。每个复合体由一个异构图表示,允许根据它们的类别(分子间或分子内)分离边缘。然后利用异构图卷积网络(HGCN),根据交叉的边缘进行信息判别。最后,该模型生成复合物的亲和度评分。结果:HGScore在评分函数比较评估(CASF) 2013和2016基准上进行了评分、排名和对接能力的测试。它超越了经典方法,成为最好的人工智能(AI)方法之一,取得了良好的性能。结论:HGScore为表达蛋白质与配体相互作用提供了一种新的方法。使用涉及经典图神经网络(gnn)的表示,并根据边缘类型划分学习过程,使所提出的模型最适合未来在其他(蛋白质- dna,蛋白质-糖,蛋白质-蛋白质等)生物复合物上的迁移学习。
{"title":"Heterogeneous graph convolutional neural network for protein-ligand scoring","authors":"Kevin Crampon, Alexis Giorkallos, X. Vigouroux, S. Baud, L. Steffenel","doi":"10.37349/eds.2023.00010","DOIUrl":"https://doi.org/10.37349/eds.2023.00010","url":null,"abstract":"Aim: Drug discovery is a long process, often taking decades of research endeavors. It is still an active area of research in both academic and industrial sectors with efforts on reducing time and cost. Computational simulations like molecular docking enable fast exploration of large databases of compounds and extract the most promising molecule candidates for further in vitro and in vivo tests. Structure-based molecular docking is a complex process mixing both surface exploration and energy estimation to find the minimal free energy of binding corresponding to the best interaction location.\u0000Methods: Hereafter, heterogeneous graph score (HGScore), a new scoring function is proposed and is developed in the context of a protein-small compound-complex. Each complex is represented by a heterogeneous graph allowing to separate edges according to their class (inter- or intra-molecular). Then a heterogeneous graph convolutional network (HGCN) is used allowing the discrimination of the information according to the edge crossed. In the end, the model produces the affinity score of the complex.\u0000Results: HGScore has been tested on the comparative assessment of scoring functions (CASF) 2013 and 2016 benchmarks for scoring, ranking, and docking powers. It has achieved good performances by outperforming classical methods and being among the best artificial intelligence (AI) methods.\u0000Conclusions: Thus, HGScore brings a new way to represent protein-ligand interactions. Using a representation that involves classical graph neural networks (GNNs) and splitting the learning process regarding the edge type makes the proposed model to be the best adapted for future transfer learning on other (protein-DNA, protein-sugar, protein-protein, etc.) biological complexes.","PeriodicalId":72998,"journal":{"name":"Exploration of drug science","volume":"50 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85736473","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}
引用次数: 0
Nano theranostics involved in bladder cancer treatment 纳米疗法在膀胱癌治疗中的应用
Pub Date : 2023-04-28 DOI: 10.37349/eds.2023.00008
Kun Liu, Qixin Mo, Z. Ding, Shicong Lai, Jian Ren, Qingsong Yu
Bladder cancer (BC) is a complex disease with multiple clinical manifestations and treatment challenges, and current standard-of-care therapies remain limited and unfavorable. Theranostics, the integration of diagnostic and therapeutic technologies, has emerged as a promising strategy to address these challenges. The rapid development of nanomedicine has been a source of hope for the improvement of BC therapies and diagnostics by reducing side effects, enhancing tumor suppression, and overcoming drug resistance. Metal nanoparticles (NPs), inorganic NPs, polymer NPs, etc. have their respective advantages and show encouraging potential in the therapy of BC. In this review, we provide an overview on the state of the art in nanotechnology-based theranostics for BC, offering insights into the design and discovery of novel NPs for future BC management.
膀胱癌(BC)是一种具有多种临床表现和治疗挑战的复杂疾病,目前的标准治疗方法仍然有限且不利。治疗学,即诊断和治疗技术的整合,已成为应对这些挑战的一种有希望的战略。纳米医学的快速发展为减少副作用、增强肿瘤抑制和克服耐药性等改善BC治疗和诊断带来了希望。金属纳米粒子(NPs)、无机纳米粒子、聚合物纳米粒子等各具优势,在BC的治疗中显示出令人鼓舞的潜力。在这篇综述中,我们概述了基于纳米技术的BC治疗的最新进展,为未来BC治疗提供了设计和发现新型NPs的见解。
{"title":"Nano theranostics involved in bladder cancer treatment","authors":"Kun Liu, Qixin Mo, Z. Ding, Shicong Lai, Jian Ren, Qingsong Yu","doi":"10.37349/eds.2023.00008","DOIUrl":"https://doi.org/10.37349/eds.2023.00008","url":null,"abstract":"Bladder cancer (BC) is a complex disease with multiple clinical manifestations and treatment challenges, and current standard-of-care therapies remain limited and unfavorable. Theranostics, the integration of diagnostic and therapeutic technologies, has emerged as a promising strategy to address these challenges. The rapid development of nanomedicine has been a source of hope for the improvement of BC therapies and diagnostics by reducing side effects, enhancing tumor suppression, and overcoming drug resistance. Metal nanoparticles (NPs), inorganic NPs, polymer NPs, etc. have their respective advantages and show encouraging potential in the therapy of BC. In this review, we provide an overview on the state of the art in nanotechnology-based theranostics for BC, offering insights into the design and discovery of novel NPs for future BC management.","PeriodicalId":72998,"journal":{"name":"Exploration of drug science","volume":"32 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85486611","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}
引用次数: 0
Machine learning for drug science 药物科学的机器学习
Pub Date : 2023-04-16 DOI: 10.37349/eds.2023.00007
de Azevedo Jr. Walter F.
Artificial intelligence (AI) has taken the daily news with increasing impact. The crescent growth of computational power and the rapid development of algorithms to harness this computational capacity delineate the perfect scenario for this avalanche of information about AI. Drug science is not immune to this influence, and many drug discovery projects employ AI. A search on PubMed using as strings “artificial intelligence” and “drug discovery” returned 1,149 publications up to 2022 (January 23, 2023). The histogram is shown Figure 1. The plot indicates a rapid increase in publications after 2018.
人工智能(AI)以越来越大的影响力占据了日常新闻。计算能力的快速增长和利用这种计算能力的算法的快速发展,描绘了关于人工智能的信息雪崩的完美场景。药物科学也不能幸免于这种影响,许多药物发现项目都采用了人工智能。在PubMed上以“人工智能”和“药物发现”作为字符串进行搜索,得到截至2022年(2023年1月23日)的1149篇论文。直方图如图1所示。该图显示了2018年之后出版物的快速增长。
{"title":"Machine learning for drug science","authors":"de Azevedo Jr. Walter F.","doi":"10.37349/eds.2023.00007","DOIUrl":"https://doi.org/10.37349/eds.2023.00007","url":null,"abstract":"Artificial intelligence (AI) has taken the daily news with increasing impact. The crescent growth of computational power and the rapid development of algorithms to harness this computational capacity delineate the perfect scenario for this avalanche of information about AI. Drug science is not immune to this influence, and many drug discovery projects employ AI. A search on PubMed using as strings “artificial intelligence” and “drug discovery” returned 1,149 publications up to 2022 (January 23, 2023). The histogram is shown Figure 1. The plot indicates a rapid increase in publications after 2018.","PeriodicalId":72998,"journal":{"name":"Exploration of drug science","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89699595","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}
引用次数: 0
期刊
Exploration of drug science
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1