Brenner S, Lerner R A
Department of Chemistry, Scripps Research Institute, La Jolla, CA 92037.
Proc Natl Acad Sci U S A. 1992 Jun 15;89(12):5381-3. doi: 10.1073/pnas.89.12.5381.
The diversity of chemical synthesis and the power of genetics are linked to provide a powerful, versatile method for drug screening. A process of alternating parallel combinatorial synthesis is used to encode individual members of a large library of chemicals with unique nucleotide sequences. After the chemical entity is bound to a target, the genetic tag can be amplified by replication and utilized for enrichment of the bound molecules by serial hybridization to a subset of the library. The nature of the chemical structure bound to the receptor is decoded by sequencing the nucleotide tag.
化学合成的多样性与遗传学的力量相结合,为药物筛选提供了一种强大且通用的方法。交替平行组合合成过程用于用独特的核苷酸序列对大量化学文库中的各个成员进行编码。在化学实体与靶标结合后,遗传标签可通过复制进行扩增,并用于通过与文库的一个子集进行系列杂交来富集结合的分子。通过对核苷酸标签进行测序来解码与受体结合的化学结构的性质。