Department of Chemistry, Duke University, Durham, NC 27708, USA.
Future Med Chem. 2009 Jul;1(4):727-36. doi: 10.4155/fmc.09.52.
The use of classical genetic and molecular biology methods along with the sequencing of many genomes has proven crucial for elucidating complex biological processes. Despite being invaluable tools, their limitations have led to a search for more versatile alternatives and, thus, to the use of small molecules. Chemical genetics is a rapidly emerging field that uses small-molecule techniques to probe biological systems and is composed of three parts: natural product or small-molecule libraries, phenotypic screening and target identification. Currently, the biggest hurdle in the overall process of chemical genetics is target identification. Efforts to overcome this obstacle have led to advances in the areas of affinity chromatography, yeast haploinsufficiency, complementary DNA (cDNA) overexpression, DNA microarray, small-molecule microarray and RNA interference (RNAi) technologies. While these technologies continue to undergo further optimization, they have been integral in the identification and/or confirmation of many cellular targets and have seen an increase in applications to the drug-development process.
使用经典的遗传和分子生物学方法以及许多基因组的测序已被证明对阐明复杂的生物过程至关重要。尽管这些方法非常有价值，但它们的局限性促使人们寻找更通用的替代方法，因此也促使人们使用小分子。化学遗传学是一个迅速发展的领域，它使用小分子技术来探测生物系统，由三个部分组成：天然产物或小分子文库、表型筛选和靶标鉴定。目前，化学遗传学整体过程中的最大障碍是靶标鉴定。为了克服这一障碍，人们在亲和层析、酵母单倍体不足、互补 DNA(cDNA)过表达、DNA 微阵列、小分子微阵列和 RNA 干扰 (RNAi) 技术等领域取得了进展。虽然这些技术仍在进一步优化，但它们在鉴定和/或确认许多细胞靶标方面发挥了重要作用，并且在药物开发过程中的应用也有所增加。
