Pillutla Renuka C, Fisher Paul B, Blume Arthur J, Goldstein Neil I
DGI Biotechnologies, Inc. 40 Talmadge Road, Edison, NJ 08818, USA.
Expert Opin Ther Targets. 2002 Aug;6(4):517-31. doi: 10.1517/14728222.6.4.517.
After the successful completion of the human genome project, mapping of the human proteome has become the next important challenge facing the biotech and pharmaceutical industries. Identification of the 'right' target(s) is now a critical part of the process because of the cost of drug discovery. Compounding this situation is the fact that the pharmaceutical industry faces a further challenge of being able to sustain current and historical growth rates. Hence, the discovery of new drug targets is important for developing new drug leads that can become preclinical drug candidates. Proteomics is the next phase of the effort whereby the human genome can be understood. However, mapping the human proteome presents a daunting challenge. Proteomics involves several essential components with the most significant being the discovery and description of all protein-protein interactions. Once this compendium is available, a secondary and equally important initiative will be to decipher proteins that are differentially expressed in any given disease condition. At this point, the critical focus will be to select the most relevant proteins, understand their partner interactions and then further winnow them to the point where they are relevant pharmaceutical target candidates. This paradigm can be compared to finding the relevant 'needle in the proteome haystack'. This review describes the use of genomic and protein-protein interaction technologies to identify and validate these 'needles' as the first step in the drug discovery process.
人类基因组计划成功完成后,绘制人类蛋白质组图谱已成为生物技术和制药行业面临的下一个重大挑战。由于药物研发成本高昂,确定“正确”的靶点如今已成为这一过程的关键部分。制药行业面临着进一步的挑战,即要能够维持当前及以往的增长率,这使得情况更加复杂。因此,发现新的药物靶点对于开发能够成为临床前候选药物的新药先导物至关重要。蛋白质组学是理解人类基因组的下一阶段工作。然而,绘制人类蛋白质组图谱面临着艰巨的挑战。蛋白质组学涉及几个关键组成部分,其中最重要的是发现和描述所有蛋白质-蛋白质相互作用。一旦获得这一蛋白质组清单,第二项同样重要的工作将是解读在任何特定疾病状态下差异表达的蛋白质。此时,关键重点将是选择最相关的蛋白质,了解它们的相互作用伙伴,然后进一步筛选,使其成为相关的药物靶点候选物。这种模式可以比作在蛋白质组的干草堆中找到相关的“针”。本综述描述了利用基因组和蛋白质-蛋白质相互作用技术来识别和验证这些“针”,作为药物研发过程的第一步。