Random Chemistry

The Utilization of high diversity molecular libraries for dtug discovery in now becoming a cnetrally important and developing set of technologies, (Balliver and Kauffman 1986, 1989,1990, Geysen et. al 1987). Om he pase decade, efforts focused on two approaches: The first is ``genetic'' and based on the generatiuon of high diversity libraries of DNA, RNA, and peptides or polypeptides by the synthsis of more or less stochadstic DNA or RNA cloned into expression vectors such aws phase display libraries, (Scott and smith, 1990, Cwirla et. al 1990, Devlin et. al (1990) or plasmids and expressed in cells, (Mandecki 1990) or more recently by in vitro amplification of DNA or RNA sequences of interest, (Turek and Gold 1990, Ellington and Szostak 1990). In all these cases, the library of interest is subjected to rounds of screening or selection assays to identify molecules of interest, such as ligands, mimetic peptides, DNA regulatory sequences, proteins or RNA sequences with catalytic activities and so forth, (Dube and Loeb 1989, Oliphant and Struhl, 1987, 1989). The genetic approach is limited to creation of ``central dogma'' sequences, DNA, RNA, and proteins. Maximum diversity libraries of interest, typically displayed on surfances such as beads ,pins, or two dimensional arrays, (Geysen 1987). Here non ``central-dogma'' molecularschemata can and have been explored, including D and L peptides, and other opolymeric building blocks, as well as DNA, RNA, and peptides.