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1.
Matej Vizovisek Dragana Ristanovic Stefano Menghini Michael G. Christiansen Simone Schuerle 《International journal of molecular sciences》2021,22(5)
In recent decades, dysregulation of proteases and atypical proteolysis have become increasingly recognized as important hallmarks of cancer, driving community-wide efforts to explore the proteolytic landscape of oncologic disease. With more than 100 proteases currently associated with different aspects of cancer development and progression, there is a clear impetus to harness their potential in the context of oncology. Advances in the protease field have yielded technologies enabling sensitive protease detection in various settings, paving the way towards diagnostic profiling of disease-related protease activity patterns. Methods including activity-based probes and substrates, antibodies, and various nanosystems that generate reporter signals, i.e., for PET or MRI, after interaction with the target protease have shown potential for clinical translation. Nevertheless, these technologies are costly, not easily multiplexed, and require advanced imaging technologies. While the current clinical applications of protease-responsive technologies in oncologic settings are still limited, emerging technologies and protease sensors are poised to enable comprehensive exploration of the tumor proteolytic landscape as a diagnostic and therapeutic frontier. This review aims to give an overview of the most relevant classes of proteases as indicators for tumor diagnosis, current approaches to detect and monitor their activity in vivo, and associated therapeutic applications. 相似文献
2.
Mri Miczi Mria Golda Balzs Kunkli Tibor Nagy Jzsef Tzsr Jnos Andrs Mtyn 《International journal of molecular sciences》2020,21(24)
The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease-19 (COVID-19) being associated with severe pneumonia. Like with other viruses, the interaction of SARS-CoV-2 with host cell proteins is necessary for successful replication, and cleavage of cellular targets by the viral protease also may contribute to the pathogenesis, but knowledge about the human proteins that are processed by the main protease (3CLpro) of SARS-CoV-2 is still limited. We tested the prediction potentials of two different in silico methods for the identification of SARS-CoV-2 3CLpro cleavage sites in human proteins. Short stretches of homologous host-pathogen protein sequences (SSHHPS) that are present in SARS-CoV-2 polyprotein and human proteins were identified using BLAST analysis, and the NetCorona 1.0 webserver was used to successfully predict cleavage sites, although this method was primarily developed for SARS-CoV. Human C-terminal-binding protein 1 (CTBP1) was found to be cleaved in vitro by SARS-CoV-2 3CLpro, the existence of the cleavage site was proved experimentally by using a His6-MBP-mEYFP recombinant substrate containing the predicted target sequence. Our results highlight both potentials and limitations of the tested algorithms. The identification of candidate host substrates of 3CLpro may help better develop an understanding of the molecular mechanisms behind the replication and pathogenesis of SARS-CoV-2. 相似文献
3.
从浏阳豆豉发酵过程中分离产高酶活菌株,通过形态观察结合分子生物学技术进行鉴定,并对其产蛋白酶、脂肪酶及纤维素酶的活性进行分析。结果表明,分离得到3株菌(编号为000、5132、621)均被鉴定为溜曲霉菌(Aspergillus tamarri)。3株菌的蛋白酶、脂肪酶及纤维素酶的活性测定结果表明,菌株621蛋白酶活性最强,为(207.98±3.20)U/mL;菌株5132的纤维素酶活性最强,为(3.40±1.40)U/mL;菌株000的脂肪酶活性最高,为(90.7±0.64)U/mL。 相似文献
4.
Dr. André L. C. S. Nascimento Richard P. Fernandes Christian Quijia Victor H. S. Araujo Juliana Pereira Prof. Dr. Jerusa S. Garcia Prof. Dr. Marcello G. Trevisan Prof. Dr. Marlus Chorilli 《ChemMedChem》2020,15(12):1018-1029
Since the beginning of the HIV epidemic, research has been carried out to control the virus. Understanding the mechanisms of replication has given access to the various classes of drugs that over time have transformed AIDS into a manageable chronic disease. The class of protease inhibitors (PIs) gained notice in anti-retroviral therapy, once it was found that peptidomimetic molecules act by blocking the active catalytic center of the aspartic protease, which is directly related to HIV maturation. However, mutations in enzymatic internal residues are the biggest issue for these drugs, because a small change in biochemical interaction can generate resistance. Low plasma concentrations of PIs favor viral natural selection; high concentrations can inhibit even partially resistant enzymes. Food-drug/drug-drug interactions can decrease the bioavailability of PIs and are related to many side effects. Therefore, this review summarizes the pharmacokinetic properties of current PIs, the changes when pharmacological boosters are used and also lists the major mutations to help understanding of how long the continuous treatment can ensure a low viral load in patients. 相似文献
5.
以小麦麸皮为原料,分别采用碱性蛋白酶法和超声波辅助碱性蛋白酶法提取麸皮淀粉,优化两种方法的提取条件,并对麸皮淀粉的颗粒结构及分子结构进行了初步测定分析。结果表明,碱性蛋白酶法最优提取条件为固液比1∶10(g∶mL),酶用量529.92 U/mL,酶作用时间50 min,反应温度45 ℃,pH 12,麸皮淀粉得率为30.40%,淀粉含量59.24%,小麦麸皮淀粉呈淡褐色粉末状。超声波辅助碱性蛋白酶法的最优条件:固液比为1∶15(g/mL),超声功率为200 W,超声时间为15 min,麸皮淀粉得率为21.06%,淀粉含量为90.64%,麸皮淀粉呈白色粉末。超声波辅助碱性蛋白酶法提取麸皮淀粉的纯度及提取率均优于碱性蛋白酶法。经测定分析小麦麸皮淀粉中支/直比为4.69,破损淀粉含量1.78%。淀粉麸皮颗粒呈椭球型,平均粒径为15.86 μm,具有径向结晶结构,为A型结晶。 相似文献
6.
通过电泳和体积排阻-高效液相色谱探究芝麻内源性蛋白酶的水解性质,在内源性蛋白酶最适的水解条件下,探究水解时间、破乳pH、固形物含量、粒径大小、蛋白质含量对破乳的影响。结果发现,芝麻粗油体中内源性蛋白酶在pH 4、50℃条件下水解速度相对最快,且在此条件下水解4 h后,破乳p H为5时破乳率高达97%。但是综合风味和破乳率的增长速度,发现2 h水解时间为最佳,破乳率可达87%。粗油体固形物含量在50%时破乳率最高。粒径越小、蛋白质含量越高,越难以破乳。实验结果为利用芝麻内源性蛋白酶进行水酶法提油提供了工艺基础。 相似文献
7.
一株芝麻香型白酒高温大曲细菌Q2B1的鉴定及其产酶活性研究 总被引:1,自引:0,他引:1
大曲细菌关系到白酒酿造的品质,其中酶的含量与活性与白酒的风味紧密关联。以芝麻香型白酒高温大曲优势细菌代表菌株Q2B1为研究对象,利用分子生物学技术对其分类学地位进行研究,并通过全基因组研究技术对产酶相关功能基因与代谢通路进行研究。结果表明,菌株Q2B1被鉴定为贝莱斯芽孢杆菌(Bacillus velezensis)。利用传统的培养技术定性定量地检测其酶活力,发现菌株Q2B1可产淀粉酶和蛋白酶,活力分别为5.852 U/mL和26.770 U/mL;其产酶相关功能基因组长度为3 475 602 bp,包括蛋白酶编码基因以及淀粉酶编码基因,在基因水平上初步揭示了Q2B1菌株合成蛋白酶和淀粉酶的分子机理,为进一步合理开发白酒大曲微生物奠定理论基础,为提高白酒品质提供科学依据。 相似文献
8.
Francesco Caruso Manrose Singh Stuart Belli Molly Berinato Miriam Rossi 《International journal of molecular sciences》2020,21(23)
We describe the potential anti coronavirus disease 2019 (COVID-19) action of the methide quinone inhibitor, celastrol. The related methide quinone dexamethasone is, so far, among COVID-19 medications perhaps the most effective drug for patients with severe symptoms. We observe a parallel redox biology behavior between the antioxidant action of celastrol when scavenging the superoxide radical, and the adduct formation of celastrol with the main COVID-19 protease. The related molecular mechanism is envisioned using molecular mechanics and dynamics calculations. It proposes a covalent bond between the S(Cys145) amino acid thiolate and the celastrol A ring, assisted by proton transfers by His164 and His41 amino acids, and a π interaction from Met49 to the celastrol B ring. Specifically, celastrol possesses two moieties that are able to independently scavenge the superoxide radical: the carboxylic framework located at ring E, and the methide-quinone ring A. The latter captures the superoxide electron, releasing molecular oxygen, and is the feature of interest that correlates with the mechanism of COVID-19 inhibition. This unusual scavenging of the superoxide radical is described using density functional theory (DFT) methods, and is supported experimentally by cyclic voltammetry and X-ray diffraction. 相似文献
9.
微生物质粒过表达外源基因,会由于质粒分离稳定性低、种子培养基中需添加抗生素等原因,限制其在工业生产中的应用。为了得到一株可用于工业生产谷氨酰胺酶的菌株,选择食品安全级Bacillus subtilis 168作为宿主,将来源于Micrococcus luteus K-3的编码耐高浓度盐的谷氨酰胺酶基因(Mglu)插入到其染色体上进行整合表达。选择了2个内源性蛋白酶基因作为整合表达位点,通过lox序列的重组消除抗性基因,得到无抗性基因的重组谷氨酰胺酶表达菌株。遗传稳定性研究表明,在不添加抗生素的条件下,通过连续传代重组菌株并测定发酵酶活,发现重组菌株连续传42代时,酶活基本不变。随后,采用5 L发酵罐对重组菌株进行分批补料发酵,最高酶活达到了41.5 U/mL。本研究对提高谷氨酰胺酶重组菌株遗传稳定性提供了借鉴。 相似文献
10.