Elrick Mollisa M, Walgren Jennie L, Mitchell Michael D, Thompson David C
Worldwide Safety Sciences, Pfizer, Inc., 700 Chesterfield Parkway West, Chesterfield, MO 63017, USA.
Basic Clin Pharmacol Toxicol. 2006 May;98(5):432-41. doi: 10.1111/j.1742-7843.2006.pto_391.x.
Interest in proteomics as a tool for drug development and a myriad of other applications continues to expand at a rapid rate. Proteomic analyses have recently been conducted on tissues, biofluids, subcellular components and enzymatic pathways as well as various disease and toxicological states, in both animal models and man. In addition, several recent studies have attempted to integrate proteomics data with genomics and/or metabonomics data in a systems biology approach. The translation of proteomic technology and bioinformatics tools to clinical samples, such as in the areas of disease and toxicity biomarkers, represents one of the major opportunities and challenges facing this field. An ongoing challenge in proteomics continues to be the analysis of the serum proteome due to the vast number and complexity of proteins estimated to be present in this biofluid. Aside from the removal of the most abundant proteins, a number of interesting approaches have recently been suggested that may help reduce the overall complexity of serum analysis. In keeping with the increasing interest in applications of proteomics, the tools available for proteomic analyses continue to improve and expand. For example, enhanced tools (such as software and labeling procedures) continue to be developed for the analysis of 2D gels and protein quantification. In addition, activity-based probes are now being used to tag, enrich and isolate distinct sets of proteins based on enzymatic activity. One of the most active areas of development involves microarrays. Antibody-based microarrays have recently been released as commercial products while numerous additional capture agents (e.g. aptamers) and many additional types of microarrays are being explored.
蛋白质组学作为药物开发及众多其他应用的一种工具,其受关注程度正持续快速扩展。近期,在动物模型和人体中,已针对组织、生物流体、亚细胞成分、酶促途径以及各种疾病和毒理学状态开展了蛋白质组学分析。此外,最近有多项研究尝试采用系统生物学方法,将蛋白质组学数据与基因组学和/或代谢组学数据整合起来。将蛋白质组学技术和生物信息学工具应用于临床样本,如疾病和毒性生物标志物领域,是该领域面临的主要机遇和挑战之一。由于估计存在于这种生物流体中的蛋白质数量众多且复杂,蛋白质组学中一个持续存在的挑战仍是血清蛋白质组的分析。除了去除含量最丰富的蛋白质外,最近还提出了一些有趣的方法,可能有助于降低血清分析的整体复杂性。随着对蛋白质组学应用的兴趣日益浓厚,可用于蛋白质组学分析的工具也在不断改进和扩展。例如,用于二维凝胶分析和蛋白质定量的增强工具(如软件和标记程序)不断得到开发。此外,基于活性的探针现在正被用于根据酶活性标记、富集和分离不同的蛋白质组。发展最为活跃的领域之一涉及微阵列。基于抗体的微阵列最近已作为商业产品推出,同时还在探索众多其他捕获剂(如适体)和许多其他类型的微阵列。