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FLT3抑制剂 1

吉瑞替尼 1

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基于质谱的免疫肽组学 1

奎扎替尼 1

急性髓系白血病 1

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环状RNA 1

米哚妥林 1

粗粒化计算 1

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Atomistic characterization of binding modes and affinity of peptide inhibitors to amyloid-

Fufeng LIU,Wenjie DU,Yan SUN,Jie ZHENG,Xiaoyan DONG

《化学科学与工程前沿（英文）》 2014年 第8卷 第4期   页码 433-444 doi: 10.1007/s11705-014-1454-6

摘要： The aggregation of amyloid -protein (A ) is tightly linked to the pathogenesis of Alzheimer’s disease. Previous studies have found that three peptide inhibitors (i.e., KLVFF, VVIA, and LPFFD) can inhibit A aggregation and alleviate A -induced neurotoxicity. However, atomic details of binding modes and binding affinities between these peptide inhibitors and A have not been revealed. Here, using molecular dynamics simulations and molecular mechanics Poisson Boltzmann surface area (MM/PBSA) analysis, we examined the effect of three peptide inhibitors (KLVFF, VVIA, and LPFFD) on their sequence-specific interactions with A and the molecular basis of their inhibition. All inhibitors exhibit varied binding affinity to A , in which KLVFF has the highest binding affinity, whereas LPFFD has the least. MM/PBSA analysis further revealed that different peptide inhibitors have different modes of interaction with A , consequently hotspot binding residues, and underlying driving forces. Specific residue-based interactions between inhibitors and A were determined and compared for illustrating different binding and inhibition mechanisms. This work provides structure-based binding information for further modification and optimization of these three peptide inhibitors to enhance their binding and inhibitory abilities against A aggregation.

关键词： Alzheimer’s disease     amyloid β-protein     peptide inhibitors     protein-protein interaction     molecular dynamics simulation    

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Cystine oligomers successfully attached to peptide cysteine-rich fibrils

Christian Bortolini,Mingdong Dong

《化学科学与工程前沿（英文）》 2016年 第10卷 第1期   页码 99-102 doi: 10.1007/s11705-016-1554-6

摘要： Amyloid peptides are renowned to be related to neurodegenerative diseases, however, a fruitful avenue is to employ them as high-performance nanomaterials. These materials benefit from the intrinsic outstanding mechanical robustness of the amyloid backbone made of -strands. In this work, we exploited amyloid-like fibrils as functional material to attach pristine L-cysteine aggregates (cystine oligomers) and gold nanoparticles, without the need of templating compounds. This work will open new avenues on functional materials design and their realisation.

关键词： cysteine     peptide fibrils     gold nanoparticles     amyloids     oligomers     nanomaterials    

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Glucagon-like peptide-2 exhibits protective effect on hepatic ischemia-reperfusion injury in rats

null

《医学前沿（英文）》 2015年 第9卷 第3期   页码 368-373 doi: 10.1007/s11684-015-0403-1

摘要：

Glucagon-like peptide-2 (GLP-2) has potent anti-inflammatory effects and protects against experimental ischemia/reperfusion (I/R) injury in pulmonary, intestinal, and myocardial tissue. However, its protective abilities against I/R injury in the liver are unknown. We investigated the potential role of GLP-2 pretreatment on hepatic I/R injury in rats. A total of 24 rats were randomly divided into three groups (n = 8). The first group was the control group; the second group was the vehicle-treated hepatic ischemia/reperfusion (HIR, vehicle saline-treated) group; and the third group was the GLP-2 pretreated I/R (GLP2-IR) group. Each rat in the third group was intraperitoneally administered 5 μg GLP-2 for 5 d before the procedure. A portal triad was created to induce ischemia with a vascular atraumatic clamp. After 40 min, the clamp was released to initiate hepatic reperfusion for 6 h. Blood samples and tissue specimens from the liver were obtained. Alanine aminotransferase, aspartate aminotransferase, and total bilirubin levels significantly increased in the saline-treated HIR group (P<0.001), whereas GLP-2 pretreatment significantly decreased their levels (P<0.01). Our data suggested that GLP-2 pretreatment may have a protective effect on liver I/R injury. However, dose-response studies are necessary to determine the most effective dose.

关键词： ischemia/reperfusion     liver     glucagon-like peptide-2     alanine aminotransferase    

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The role of natriuretic peptide precursor A gene polymorphism in the development of coronary heart disease

Ripen NSENGA MD, Longxian CHENG PhD, Mei’an HE PhD, Tangchun WU PhD,

《医学前沿（英文）》 2009年 第3卷 第4期   页码 437-442 doi: 10.1007/s11684-009-0074-x

摘要： Natriuretic peptide precursor A (NPPA) is synthesized, stored, and released by atrial myocytes. Previous studies have shown that NPPA plays a significant role in the regulation of coronary circulation and in atherosclerosis. Rs5065 NPPA gene polymorphism leads to the translation of NPPA with two additional arginines and has been suggested to be associated with salt-sensitive hypertension. The purpose of the present study was to investigate the relationship between the rs5065 NPPA gene polymorphism and the risk of coronary heart disease (CHD) in Chinese Han population. We genotyped the single nucleotide polymorphism (SNP) rs5065 NPPA in the human NPPA gene in 1861 sex- and age-matched subjects, comprising of 904 CHD cases and 957 controls of Chinese Han population. Genotyping of SNP was performed with Taqman SNP allelic discrimination assays by means of an ABI 7900HT. Our study showed that the frequencies of rs5065 NPPA C allele in the case and the control groups were 0.012 and 0.005, respectively. There was significant difference in C allele frequency distribution between the two groups (OR=2.607, 95% CI: 1.197−5.678, =0.012). In the case group, there was significant difference between smokers and nonsmokers with subjects carrying C allele (=0.037), and no significant difference in gender, age, fasting total cholesterol (TC), triglycerides (TG), fasting plasma glucose (FPG), body mass index (BMI), and blood pressure (BP) between the cases and the controls (>0.05). Our results suggest that the C allele of rs5065 NPPA gene polymorphism may be associated with the risk of CHD.

关键词： natriuretic peptide precursor A     coronary heart disease     gene polymorphism     allelic discrimination     polymorphism     single nucleotide    

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Synthesis of mono and bis-4-methylpiperidiniummethyl-urea as corrosion inhibitors for steel in acidic

Abbas TEIMOURI, Nasrin SOLTANI, Alireza Najafi CHERMAHINI

《化学科学与工程前沿（英文）》 2011年 第5卷 第1期   页码 43-50 doi: 10.1007/s11705-010-0532-7

摘要： Mono and bis-4-methylpiperidiniummethyl urea were synthesized, characterized and used as new corrosion inhibitors of mild steel in the acidic media. Inhibitory effect of two compounds on mild steel surface in the 1 mol·L sulphuric acid has been studied by a series of techniques, such as potentiodynamic polarization, weight loss and quantum chemical calculation methods. Potentiodynamic polarization measurements showed that two inhibitors are mixed type. All measurements showed that inhibition efficiencies enhanced with increase of inhibitor concentration. This reveals that inhibitive actions of inhibitors were mainly due to adsorption on mild steel surface. Density functional (DFT) calculations have been carried out for the title compounds by performing HF and DFT levels of theory using the standard 6-31G* basis set.

关键词： corrosion inhibitors     mild steel     acidic medium     theoretical studies     DFT    

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Mitogen-activated protein kinase pathway inhibitors: inhibitors for diseases?

Xu WANG MS, Xiao-Wei GONG MD, PhD, Yong JIANG MD, PhD, Yu-Hua LI PhD,

《医学前沿（英文）》 2010年 第4卷 第1期   页码 46-53 doi: 10.1007/s11684-010-0010-0

摘要： Mitogen-activated protein kinase (MAPK) signaling pathway, one of the most important signaling pathways in eukaryotic organism, is involved in multiple cellular events such as cell growth, differentiation, and apoptosis. MAPK is of great importance to the normal function of organisms, while its dysfunction results in various diseases. So far, inhibitors specifically against each subfamilies of MAP kinase have been developed, while more endeavors are needed to discover the compounds selectively targeting a particular subfamily member. Most of the kinase inhibitors exert their functions in an ATP-competitive way or a non-ATP-competitive way. Further studies on the effective mechanism of the MAPK inhibitors and their therapeutic roles in the treatment of diseases are helpful for the illumination of MAP kinase function, the development of novel inhibitors, and the therapy of diseases caused by the dysfunction of the MAPK pathway.

关键词： mitogen-activated protein kinase     drug target     inhibitor     signal transduction     disease    

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Screening responsive or resistant biomarkers of immune checkpoint inhibitors based on online databases

Zhen Xiang, Yingyan Yu

《医学前沿（英文）》 2019年 第13卷 第1期   页码 24-31 doi: 10.1007/s11684-019-0679-7

摘要： Immune checkpoint inhibitors are a promising strategy in the treatment of cancer, especially advanced types. However, not all patients are responsive to immune checkpoint inhibitors. The response rate depends on the immune microenvironment, tumor mutational burden (TMB), expression level of immune checkpoint proteins, and molecular subtypes of cancers. Along with the Cancer Genome Project, various open access databases, including The Cancer Genome Atlas and Gene Expression Omnibus, provide large volumes of data, which allow researchers to explore responsive or resistant biomarkers of immune checkpoint inhibitors. In this review, we introduced some methodologies on database selection, biomarker screening, current progress of immune checkpoint blockade in solid tumor treatment, possible mechanisms of drug resistance, strategies of overcoming resistance, and indications for immune checkpoint inhibitor therapy.

关键词： immune checkpoint blockade     sensitivity     resistance     data mining    

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Analysis of interactions of immune checkpoint inhibitors with antibiotics in cancer therapy

《医学前沿（英文）》 2022年 第16卷 第3期   页码 307-321 doi: 10.1007/s11684-022-0927-0

摘要： The discovery of immune checkpoint inhibitors, such as PD-1/PD-L1 and CTLA-4, has played an important role in the development of cancer immunotherapy. However, immune-related adverse events often occur because of the enhanced immune response enabled by these agents. Antibiotics are widely applied in clinical treatment, and they are inevitably used in combination with immune checkpoint inhibitors. Clinical practice has revealed that antibiotics can weaken the therapeutic response to immune checkpoint inhibitors. Studies have shown that the gut microbiota is essential for the interaction between immune checkpoint inhibitors and antibiotics, although the exact mechanisms remain unclear. This review focuses on the interactions between immune checkpoint inhibitors and antibiotics, with an in-depth discussion about the mechanisms and therapeutic potential of modulating gut microbiota, as well as other new combination strategies.

关键词： tumor immunotherapy     immune checkpoint inhibitor     antibiotics     gut microbiota     drug–drug interaction    

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Advances in newly developing therapy for chronic hepatitis C virus infection

null

《医学前沿（英文）》 2014年 第8卷 第2期   页码 166-174 doi: 10.1007/s11684-014-0334-2

摘要：

Chronic hepatitis C virus (HCV) infection afflicts a reported 170 million people worldwide and is often complicated by cirrhosis and hepatocellular carcinoma. Morbidity and mortality are decreased with the successful treatment of chronic HCV infection. Increased understanding of the HCV has allowed further development of new direct-acting antiviral (DAA) agents against the HCV and has also allowed the development of IFN-free oral treatment regimens. In late 2013 the first nucleotide polymerase inhibitor regimen with RBV alone for genotypes 2/3 and in combination with a 12-week regimen of PEG-IFN+RBV for genotypes 1, 4 was approved for use in the US. A number of promising new DAA regimens which are IFN-free are in phase 3 development and the first will likely be approved for use in the US in 2014. The currently approved regimens are discussed in detail and currently available data on future regimens are reviewed herein.

关键词： direct-acting antiviral (DAA)     nucleotide polymerase inhibitors     protease inhibitors    

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DISCOVERY OF TRIKETONE-QUINOXALINE HYBRIDS AS POTENT HPPD INHIBITORS USING STRUCTURE-BASED DRUG DESIGN

《农业科学与工程前沿（英文）》 2022年 第9卷 第1期   页码 133-145 doi: 10.15302/J-FASE-2021401

摘要：

p-Hydroxyphenylpyruvate dioxygenase (EC 1.13.11.27, HPPD) belongs to the family of Fe(II)-dependent non-heme oxygenases that occur in the majority of aerobic organisms. HPPD has proved to be a promising target in herbicide research and development. A battery of novel triketone-quinoxaline compounds has been designed using a structure-based drug design strategy and then prepared. Enzyme inhibition assays show that these synthesized derivatives possess favorable inhibition capability against Arabidopsis thaliana HPPD with IC50 values ranging from 0.317 to 0.891 μmol·L−1. Subsequently, the molecular docking results indicate that two adjacent carbonyls of the triketone moiety of the representative compound 2-(2,3-dimethyl-8-(o-tolyl)quinoxaline-6-carbonyl)-3-hydroxycyclohex-2-en-1-one (7d) engage in chelation with the ferrous ion of A. thaliana HPPD in a bidentate pose, and its quinoxaline scaffold forms two sets of parallel π-stacking interaction between two phenylalanine residues (Phe424 and Phe381). In addition, the extended phenyl group also interacts with Phe392 in a π-π stacking way. This study indicates that triketone-quinoxaline is a promising scaffold for discovering HPPD inhibitors with substantially increased potency, providing insight into the molecular design of new herbicides.

 

关键词： herbicide / HPPD / inhibitor / quinoxaline / triketon    

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Overcoming oral insulin delivery barriers: application of cell penetrating peptide and silica-based nanoporous

Huining HE, Junxiao YE, Jianyong SHENG, Jianxin WANG, Yongzhuo HUANG, Guanyi CHEN, Jingkang WANG, Victor C YANG

《化学科学与工程前沿（英文）》 2013年 第7卷 第1期   页码 9-19 doi: 10.1007/s11705-013-1306-9

摘要： Oral insulin delivery has received the most attention in insulin formulations due to its high patient compliance and, more importantly, to its potential to mimic the physiologic insulin secretion seen in non-diabetic individuals. However, oral insulin delivery has two major limitations: the enzymatic barrier that leads to rapid insulin degradation, and the mucosal barrier that limits insulin’s bioavailability. Several approaches have been actively pursued to circumvent the enzyme barrier, with some of them receiving promising results. Yet, thus far there has been no major success in overcoming the mucosal barrier, which is the main cause in undercutting insulin’s oral bioavailability. In this review of our group’s research, an innovative silica-based, mucoadhesive oral insulin formulation with encapsulated-insulin/cell penetrating peptide (CPP) to overcome both enzyme and mucosal barriers is discussed, and the preliminary and convincing results to confirm the plausibility of this oral insulin delivery system are reviewed. In vitro studies demonstrated that the CPP-insulin conjugates could facilitate cellular uptake of insulin while keeping insulin’s biologic functions intact. It was also confirmed that low molecular weight protamine (LMWP) behaves like a CPP peptide, with a cell translocation potency equivalent to that of the widely studied TAT. The mucoadhesive properties of the produced silica-chitosan composites could be controlled by varying both the pH and composition; the composite consisting of chitosan (25 wt-%) and silica (75 wt-%) exhibited the greatest mucoadhesion at gastric pH. Furthermore, drug release from the composite network could also be regulated by altering the chitosan content. Overall, the universal applicability of those technologies could lead to development of a generic platform for oral delivery of many other bioactive compounds, especially for peptide or protein drugs which inevitably encounter the poor bioavailability issues.

关键词： insulin     cell penetrating peptide     mucoadhesive composites     oral delivery    

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Monitoring checkpoint inhibitors: predictive biomarkers in immunotherapy

Min Zhang, Jingwen Yang, Wenjing Hua, Zhong Li, Zenghui Xu, Qijun Qian

《医学前沿（英文）》 2019年 第13卷 第1期   页码 32-44 doi: 10.1007/s11684-018-0678-0

摘要：

Immunotherapy has become the fourth cancer therapy after surgery, chemotherapy, and radiotherapy. In particular, immune checkpoint inhibitors are proved to be unprecedentedly in increasing the overall survival rates of patients with refractory cancers, such as advanced melanoma, non-small cell lung cancer, and renal cell carcinoma. However, inhibitor therapies are only effective in a small proportion of patients with problems, such as side effects and high costs. Therefore, doctors urgently need reliable predictive biomarkers for checkpoint inhibitor therapies to choose the optimal therapies. Here, we review the biomarkers that can serve as potential predictors of the outcomes of immune checkpoint inhibitor treatment, including tumor-specific profiles and tumor microenvironment evaluation and other factors.

关键词： immune checkpoint     companion diagnosis     PD-L1     tumor mutation burden     immune score    

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Development of small-molecule viral inhibitors targeting various stages of the life cycle of emerging

null

《医学前沿（英文）》 2017年 第11卷 第4期   页码 449-461 doi: 10.1007/s11684-017-0589-5

摘要：

In recent years, unexpected outbreaks of infectious diseases caused by emerging and re-emerging viruses have become more frequent, which is possibly due to environmental changes. These outbreaks result in the loss of life and economic hardship. Vaccines and therapeutics should be developed for the prevention and treatment of infectious diseases. In this review, we summarize and discuss the latest progress in the development of small-molecule viral inhibitors against highly pathogenic coronaviruses, including severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome coronavirus, Ebola virus, and Zika virus. These viruses can interfere with the specific steps of viral life cycle by blocking the binding between virus and host cells, disrupting viral endocytosis, disturbing membrane fusion, and interrupting viral RNA replication and translation, thereby demonstrating potent therapeutic effect against various emerging and re-emerging viruses. We also discuss some general strategies for developing small-molecule viral inhibitors.

关键词： emerging and re-emerging viruses     small-molecule inhibitor     coronavirus     Ebola virus     Zika virus     life cycle    

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Rational Design of and Mechanism Insight into an Efficient Antifreeze Peptide for Cryopreservation

Haishan Qi,Yihang Gao,Lin Zhang,Zhongxin Cui,Xiaojie Sui,Jianfan Ma,Jing Yang,Zhiquan Shu,Lei Zhang,

《工程（英文）》 doi: 10.1016/j.eng.2023.01.015

摘要： The development of effective antifreeze peptides to control ice growth has attracted a significant amount of attention yet still remains a great challenge. Here, we propose a novel design method based on an in-depth investigation of repetitive motifs in various ice-binding proteins (IBPs) with an evolution analysis. In this way, several peptides with notable antifreeze activity were developed. In particular, a designed antifreeze peptide named AVD exhibits ideal ice recrystallization inhibition (IRI), solubility, and biocompatibility, making it suitable for use as a cryoprotective agent (CPA). A mutation analysis and molecular dynamics (MD) simulations indicated that the Thr6 and Asn8 residues of the AVD peptide are fundamental to its ice-binding capacity, while the Ser18 residue can synergistically enhance their interaction with ice, revealing the antifreeze mechanism of AVD. Furthermore, to demonstrate the cryoprotection potential of AVD, the peptide was successfully employed for the cryopreservation of various cells, which demonstrated significant post-freezing cell recovery. This work opens up a new avenue for designing antifreeze materials and provides peptide-based functional modules for synthetic biology.

关键词： Antifreeze peptides     Evolution analysis     Ice recrystallization inhibition     Molecular dynamics simulation     Cryopreservation     Synthetic biology    

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电中性固体表面上多条肽链的吸附过程——粗粒化模拟研究 Research

裘若桑, 肖杰, 陈晓东

《工程（英文）》 2020年 第6卷 第2期   页码 185-194 doi: 10.1016/j.eng.2018.12.012

摘要：

蛋白质在固体表面的吸附过程涉及诸多复杂的分子间相互作用，因此到目前为止仍然无法做到精准调控。通过模拟计算，可以获取固-液界面分子尺度的蛋白质移动机理，从而为预测蛋白质吸附和结垢现象提供可靠的理论依据。本研究通过多尺度粗粒化模型对多条疏水的丙氨酸十二肽在金表面的聚集和吸附过程进行了分析。大约有一半（46.6%）的丙氨酸十二肽可以组成聚集体。30.0%的独立肽链会被快速地吸附到固体表面。这些在表面吸附的肽链经过一段时间的爬行，其中的一些（51.0%）能与吸附在表面的或是游离在溶液中的肽链融合，从而形成吸附在表面的聚集体。这些在固-液界面吸附的肽链使得固体表面性质发生变化。这一变化可能会进一步影响之后溶液中肽链和聚集体在金表面的吸附。本研究揭示的多条肽链吸附机理有希望为进一步研究多个蛋白质分子在固体表面的吸附机理提供理论基础。

关键词： 肽链     聚集体     吸附     粗粒化计算    

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标题 作者 时间 类型 操作

Atomistic characterization of binding modes and affinity of peptide inhibitors to amyloid-

Fufeng LIU,Wenjie DU,Yan SUN,Jie ZHENG,Xiaoyan DONG

期刊论文

Cystine oligomers successfully attached to peptide cysteine-rich fibrils

Christian Bortolini,Mingdong Dong

期刊论文

Glucagon-like peptide-2 exhibits protective effect on hepatic ischemia-reperfusion injury in rats

null

期刊论文

The role of natriuretic peptide precursor A gene polymorphism in the development of coronary heart disease

Ripen NSENGA MD, Longxian CHENG PhD, Mei’an HE PhD, Tangchun WU PhD,

期刊论文

Synthesis of mono and bis-4-methylpiperidiniummethyl-urea as corrosion inhibitors for steel in acidic

Abbas TEIMOURI, Nasrin SOLTANI, Alireza Najafi CHERMAHINI

期刊论文

Mitogen-activated protein kinase pathway inhibitors: inhibitors for diseases?

Xu WANG MS, Xiao-Wei GONG MD, PhD, Yong JIANG MD, PhD, Yu-Hua LI PhD,

期刊论文

Screening responsive or resistant biomarkers of immune checkpoint inhibitors based on online databases

Zhen Xiang, Yingyan Yu

期刊论文

Analysis of interactions of immune checkpoint inhibitors with antibiotics in cancer therapy

期刊论文

Advances in newly developing therapy for chronic hepatitis C virus infection

null

期刊论文

DISCOVERY OF TRIKETONE-QUINOXALINE HYBRIDS AS POTENT HPPD INHIBITORS USING STRUCTURE-BASED DRUG DESIGN

期刊论文

Overcoming oral insulin delivery barriers: application of cell penetrating peptide and silica-based nanoporous

Huining HE, Junxiao YE, Jianyong SHENG, Jianxin WANG, Yongzhuo HUANG, Guanyi CHEN, Jingkang WANG, Victor C YANG

期刊论文

Monitoring checkpoint inhibitors: predictive biomarkers in immunotherapy

Min Zhang, Jingwen Yang, Wenjing Hua, Zhong Li, Zenghui Xu, Qijun Qian

期刊论文

Development of small-molecule viral inhibitors targeting various stages of the life cycle of emerging

null

期刊论文

Rational Design of and Mechanism Insight into an Efficient Antifreeze Peptide for Cryopreservation

Haishan Qi,Yihang Gao,Lin Zhang,Zhongxin Cui,Xiaojie Sui,Jianfan Ma,Jing Yang,Zhiquan Shu,Lei Zhang,

期刊论文

电中性固体表面上多条肽链的吸附过程——粗粒化模拟研究

裘若桑, 肖杰, 陈晓东

期刊论文