Dervan Peter B, Doss Raymond M, Marques Michael A
Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
Curr Med Chem Anticancer Agents. 2005 Jul;5(4):373-87. doi: 10.2174/1568011054222346.
Mapping and sequencing the genetic blueprint in human, mice, yeast and other model organisms has created challenges and opportunities for chemistry, biology and human medicine. An understanding of the function of each of the approximately 25,000 genes in humans, and the biological circuitry that controls these genes will be driven in part by new technologies from the world of chemistry. Many cellular events that lead to cancer and the progression of human disease represent aberrant gene expression. Small molecules that can be programmed to mimic transcription factors and bind a large repertoire of DNA sequences in the human genome would be useful tools in biology and potentially in human medicine. Polyamides are synthetic oligomers programmed to read the DNA double helix. They are cell permeable, bind chromatin and have been shown to downregulate endogenous genes in cell culture.
绘制和测序人类、小鼠、酵母及其他模式生物的基因蓝图，给化学、生物学和人类医学带来了挑战与机遇。了解人类约25000个基因中每个基因的功能，以及控制这些基因的生物回路，将部分由化学领域的新技术推动。许多导致癌症和人类疾病进展的细胞事件代表着异常的基因表达。能够被编程以模拟转录因子并结合人类基因组中大量DNA序列的小分子，将成为生物学乃至人类医学中的有用工具。聚酰胺是被编程用于读取DNA双螺旋的合成寡聚物。它们具有细胞渗透性，能结合染色质，并且已被证明可在细胞培养中下调内源性基因。
