Drug Discovery Today: Technologies最新文献_第2页

Generation of bispecific antibodies using chemical conjugation methods 使用化学偶联法生成双特异性抗体

Drug Discovery Today: Technologies Pub Date : 2021-12-01 DOI: 10.1016/j.ddtec.2021.08.006

Nazzareno Dimasi , Amit Kumar , Changshou Gao

引用次数: 7

Design of mammalian cell-based biotechnology plants 哺乳动物细胞生物技术植物的设计

Drug Discovery Today: Technologies Pub Date : 2021-12-01 DOI: 10.1016/j.ddtec.2021.08.004

David Domonkos , Kalman Könczöl , Imre Török

引用次数: 0

Quantitative proteomics in drug discovery and development 定量蛋白质组学在药物研发中的应用

Drug Discovery Today: Technologies Pub Date : 2021-12-01 DOI: 10.1016/j.ddtec.2021.10.003

Bhagwat Prasad

引用次数: 0

Potential of X-ray free-electron lasers for challenging targets in structure-based drug discovery x射线自由电子激光器在基于结构的药物发现中具有挑战性目标的潜力

Drug Discovery Today: Technologies Pub Date : 2021-12-01 DOI: 10.1016/j.ddtec.2021.08.002

Gabriela Nass Kovacs

{"title":"Potential of X-ray free-electron lasers for challenging targets in structure-based drug discovery","authors":"Gabriela Nass Kovacs","doi":"10.1016/j.ddtec.2021.08.002","DOIUrl":"10.1016/j.ddtec.2021.08.002","url":null,"abstract":"<div><p>X-ray crystallography has provided the vast majority of three-dimensional macromolecular structures. Most of these are high-resolution structures that enable a detailed understanding of the underlying molecular mechanisms. The standardized workflows and robust infrastructure of synchrotron-based macromolecular crystallography (MX) offer the high throughput essential to cost-conscious investigations in structure- and fragment-based drug discovery. Nonetheless conventional MX is limited by fundamental bottlenecks, in particular X-ray radiation damage, which limits the amount of data extractable from a crystal. While this limit can in principle be circumvented by using larger crystals, crystals of the requisite size often cannot be obtained in sufficient quality. That is especially true for membrane protein crystals, which constitute the majority of current drug targets. This conventional paradigm for MX-suitable samples changed dramatically with the advent of serial femtosecond crystallography (SFX) based on the ultra-short and extremely intense X-ray pulses of X-ray Free-Electron Lasers. SFX provides high-resolution structures from tiny crystals and does so with uniquely low levels of radiation damage. This has yielded a number of novel structures for G-protein coupled receptors, one of the most relevant membrane protein superfamilies for drug discovery, as well as tantalizing advances in time-resolved crystallography that elucidate protein dynamics. This article attempts to map the potential of SFX for drug discovery, while providing the reader with an overview of the yet remaining technical challenges associated with such a novel technique as SFX.</p></div>","PeriodicalId":36012,"journal":{"name":"Drug Discovery Today: Technologies","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1740674921000196/pdfft?md5=af93a3f2a0f5810949f85fc981018e4e&pid=1-s2.0-S1740674921000196-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39725779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 5

Mass spectrometry based approaches and strategies in bioanalysis for qualitative and quantitative analysis of pharmaceutically relevant molecules 生物分析中基于质谱的方法和策略，用于药物相关分子的定性和定量分析

Drug Discovery Today: Technologies Pub Date : 2021-12-01 DOI: 10.1016/j.ddtec.2021.10.004

Frank Klont, Gérard Hopfgartner

引用次数: 1

Advances in sample preparation for membrane proteome quantification 膜蛋白质组定量样品制备研究进展

Drug Discovery Today: Technologies Pub Date : 2021-12-01 DOI: 10.1016/j.ddtec.2021.06.005

Takeshi Masuda, Shingo Ito, Sumio Ohtsuki

引用次数: 4

Recent advances in mass-spectrometry based proteomics software, tools and databases 基于质谱的蛋白质组学软件、工具和数据库的最新进展

Drug Discovery Today: Technologies Pub Date : 2021-12-01 DOI: 10.1016/j.ddtec.2021.06.007

Ankit Halder, Ayushi Verma, Deeptarup Biswas, Sanjeeva Srivastava

{"title":"Recent advances in mass-spectrometry based proteomics software, tools and databases","authors":"Ankit Halder, Ayushi Verma, Deeptarup Biswas, Sanjeeva Srivastava","doi":"10.1016/j.ddtec.2021.06.007","DOIUrl":"10.1016/j.ddtec.2021.06.007","url":null,"abstract":"<div><p>The field of proteomics<span> immensely depends on data generation and data analysis which are thoroughly supported by software and databases. There has been a massive advancement in mass spectrometry-based proteomics over the last 10 years which has compelled the scientific community to upgrade or develop algorithms, tools, and repository databases in the field of proteomics. Several standalone software, and comprehensive databases have aided the establishment of integrated omics<span> pipeline and meta-analysis workflow which has contributed to understand the disease pathobiology, biomarker discovery<span> and predicting new therapeutic modalities. For shotgun proteomics where Data Dependent Acquisition is performed, several user-friendly software are developed that can analyse the pre-processed data to provide mechanistic insights of the disease. Likewise, in Data Independent Acquisition, pipelines are emerged which can accomplish the task from building the spectral library to identify the therapeutic targets. Furthermore, in the age of big data analysis the implications of machine learning and cloud computing are appending robustness, rapidness and in-depth proteomics data analysis. The current review talks about the recent advancement, and development of software, tools, and database in the field of mass-spectrometry based proteomics.</span></span></span></p></div>","PeriodicalId":36012,"journal":{"name":"Drug Discovery Today: Technologies","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39587152","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: 11

Rapid visualization of lipopeptides and potential bioactive groups of compounds by combining ion mobility and MALDI imaging mass spectrometry 结合离子迁移率和MALDI成像质谱法快速可视化脂肽和化合物的潜在生物活性基团

Drug Discovery Today: Technologies Pub Date : 2021-12-01 DOI: 10.1016/j.ddtec.2021.08.003

Andréa McCann , Christopher Kune , Raphael La Rocca , Janina Oetjen , Anthony Arguelles Arias , Marc Ongena , Johann Far , Gauthier Eppe , Loic Quinton , Edwin De Pauw

{"title":"Rapid visualization of lipopeptides and potential bioactive groups of compounds by combining ion mobility and MALDI imaging mass spectrometry","authors":"Andréa McCann , Christopher Kune , Raphael La Rocca , Janina Oetjen , Anthony Arguelles Arias , Marc Ongena , Johann Far , Gauthier Eppe , Loic Quinton , Edwin De Pauw","doi":"10.1016/j.ddtec.2021.08.003","DOIUrl":"10.1016/j.ddtec.2021.08.003","url":null,"abstract":"<div><p><span><span>Mass spectrometry imaging<span> (MSI) has become a powerful method for mapping metabolite distribution in a tissue. Applied to bacterial colonies<span>, MSI has a bright future, both for the discovery of new bioactive compounds and for a better understanding of bacterial antibiotic resistance mechanisms. Coupled with separation techniques such as </span></span></span>ion mobility mass spectrometry<span> (IM-MS), the identification of metabolites directly on the image is now possible and does not require additional analysis such as HPLC-MS/MS. In this article, we propose to apply a semi-targeted workflow for rapid IM-MSI data analysis focused on the search for bioactive compounds. First, chemically-related compounds showing a repetitive mass unit (i.e. lipids and lipopeptides) were targeted based on the Kendrick mass defect analysis. The detected groups of potentially bioactive compounds were then confirmed by fitting their measured ion moibilites to their measured </span></span><em>m/z</em> values. Using both their <em>m/z</em><span> and ion mobility values, the selected groups of compounds were identified using the available databases and finally their distribution was observed on the image. Using this workflow on a co-culture of bacteria, we were able to detect and localize bioactive compounds involved in the microbial interaction.</span></p></div>","PeriodicalId":36012,"journal":{"name":"Drug Discovery Today: Technologies","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ddtec.2021.08.003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39587153","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: 4

In a flash of light: X-ray free electron lasers meet native mass spectrometry 一闪而过:x射线自由电子激光器与天然质谱法相遇

Drug Discovery Today: Technologies Pub Date : 2021-12-01 DOI: 10.1016/j.ddtec.2021.07.001

Alan Kadek , Kristina Lorenzen , Charlotte Uetrecht , for MS SPIDOC consortium

{"title":"In a flash of light: X-ray free electron lasers meet native mass spectrometry","authors":"Alan Kadek , Kristina Lorenzen , Charlotte Uetrecht , for MS SPIDOC consortium","doi":"10.1016/j.ddtec.2021.07.001","DOIUrl":"10.1016/j.ddtec.2021.07.001","url":null,"abstract":"<div><p>During the last years, X-ray free electron lasers (XFELs) have emerged as X-ray sources of unparalleled brightness, delivering extreme amounts of photons in femtosecond pulses. As such, they have opened up completely new possibilities in drug discovery and structural biology, including studying high resolution biomolecular structures and their functioning in a time resolved manner, and diffractive imaging of single particles without the need for their crystallization. In this perspective, we briefly review the operation of XFELs, their immediate uses for drug discovery and focus on the potentially revolutionary single particle diffractive imaging technique and the challenges which remain to be overcome to fully realize its potential to provide high resolution structures without the need for crystallization, freezing or the need to keep proteins stable at extreme concentrations for long periods of time. As the issues have been to a large extent sample delivery related, we outline a way for native mass spectrometry to overcome these and enable so far impossible research with a potentially huge impact on structural biology and drug discovery, such as studying structures of transient intermediate species in viral life cycles or during functioning of molecular machines.</p></div>","PeriodicalId":36012,"journal":{"name":"Drug Discovery Today: Technologies","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ddtec.2021.07.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39587154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 5

Drug discovery from natural products using affinity selection-mass spectrometry 利用亲和选择-质谱法从天然产物中发现药物

Drug Discovery Today: Technologies Pub Date : 2021-12-01 DOI: 10.1016/j.ddtec.2021.10.005

Ruth N. Muchiri , Richard B. van Breemen

{"title":"Drug discovery from natural products using affinity selection-mass spectrometry","authors":"Ruth N. Muchiri , Richard B. van Breemen","doi":"10.1016/j.ddtec.2021.10.005","DOIUrl":"10.1016/j.ddtec.2021.10.005","url":null,"abstract":"<div><p>As a starting point for drug discovery<span><span><span>, affinity selection-mass spectrometry (AS-MS) is ideal for the discovery of lead compounds from chemically diverse sources such as botanical, fungal and microbial extracts. Based on binding interactions between macromolecular receptors and ligands of low molecular mass, AS-MS enables the rapid isolation of pharmacologically active small molecules<span><span> from complex mixtures for mass spectrometric characterization and identification. Unlike conventional high-throughput screening, AS-MS requires no radiolabels, no UV or fluorescent chromophores, and is compatible with all classes of receptors, </span>enzymes, incubation buffers, cofactors, and ligands. The most successful types of AS-MS include pulsed </span></span>ultrafiltration (PUF) AS-MS, size exclusion chromatography (SEC) AS-MS, and magnetic microbead affinity selection screening (MagMASS), which differ in their approaches for separating the ligand-receptor complexes from the non-binding compounds in mixtures. After affinity isolation, the ligand(s) from the mixture are characterized using high resolution UHPLC-MS and </span>tandem mass spectrometry. Based on these elemental composition and structural data, the identities of the lead compounds are determined by searching on-line databases for known natural products and by comparison with standards. The structures of novel natural products are determined using a combination of spectroscopic techniques including two-dimensional NMR and MS.</span></p></div>","PeriodicalId":36012,"journal":{"name":"Drug Discovery Today: Technologies","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39820740","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: 7