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蛋白质组学研究揭示了小分子疗法的重要信息:以血浆蛋白为例的一项案例研究。

Proteomics studies reveal important information on small molecule therapeutics: a case study on plasma proteins.

作者信息

Zolla Lello

机构信息

Department of Environmental Science, University of Tuscia, Piazzale Università, Viterbo, Italy.

出版信息

Drug Discov Today. 2008 Dec;13(23-24):1042-51. doi: 10.1016/j.drudis.2008.09.013. Epub 2008 Nov 7.

Abstract

The most abundant proteins in serum, such as albumin and IgG, act as molecular sponges that bind and transport low molecular weight proteins/peptides and drugs. In the near future, pharmacoproteomics, the use of proteomic technologies in the field of drug discovery and development, and interactomics, the branch of proteomics which is concerned with identifying interactions between proteins, will allow researchers to (i) know the specific protein changes that occur in biological compartments in response to drug administration; (ii) design small novel therapeutic molecules that can have extended half-lives if carried by plasma protein in the blood stream. Advances in these fields will open new avenues of tailor-made molecular therapy, reducing present limitations on treatment arising from toxicity and inefficiency. In this short review we report and discuss the most recent developments arising from the use of proteomic tools in blood plasma protein research, looking at the identification of proteins found in plasma as well as their interactions with small molecules such as drugs, peptides, organic chemicals and metals. We believe this research demonstrates that proteomic technologies, and in particular pharmacoproteomics, interactomics and post-translational modification analysis, could be instrumental in the design of new tailor-made drugs leading to substantial improvements in molecular therapy.

摘要

血清中含量最丰富的蛋白质,如白蛋白和免疫球蛋白G,起着分子海绵的作用,可结合并转运低分子量蛋白质/肽以及药物。在不久的将来,药物蛋白质组学(即在药物发现与开发领域应用蛋白质组学技术)和相互作用组学(蛋白质组学中关注鉴定蛋白质之间相互作用的分支领域)将使研究人员能够:(i)了解生物区室中因给药而发生的特定蛋白质变化;(ii)设计新型小分子治疗药物,如果这些药物由血浆蛋白携带进入血流,其半衰期可能会延长。这些领域的进展将开辟定制分子治疗的新途径,减少目前因毒性和低效性导致的治疗局限性。在这篇简短的综述中,我们报告并讨论了在血浆蛋白研究中使用蛋白质组学工具所取得的最新进展,着眼于血浆中蛋白质的鉴定以及它们与药物、肽、有机化学品和金属等小分子之间的相互作用。我们认为这项研究表明,蛋白质组学技术,尤其是药物蛋白质组学、相互作用组学和翻译后修饰分析,可能有助于设计新的定制药物,从而在分子治疗方面取得实质性进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c04b/7185545/bbcac78ec304/gr1.jpg

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