Synthetic receptor binding elucidated with an encoded combinatorial library
Synthetic receptor binding elucidated with an encoded combinatorial library
复制标题
用编码组合库阐明合成受体结合
DOI：
10.1021/ja00080a044
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发表时间：
1994
影响因子：
15
通讯作者：
W. Still
中科院分区：
文献类型：
--
作者：
A. Borchardt;W. Still
For more than a decade, researchers have studied thebinding of synthetic receptors and substrates to learn about molecular complexation. But because binding studies are labor intensive, a small number of binding measurements are usually carried out and often uncover only those binding phenomena explicitly sought. In this communication, we describe an alternative method for evaluating binding using librariesof substrates. 1 We show that the method not only allows the screening of> 50 000-member substrate librariesfor binding but also can uncover selectivities that would be very difficult to find using traditional means. Our assay involves linking a receptor (eg, 1) to a dye and then adding a library of substrates attached to Merrifield beads. Beads bearing substrates which tightly bind the receptor will become colored. The only difficulty is in determining the structure of the 10-100 pmol of substrate on each colored bead. 2 To solve this problem, we use a binary-encoded combinatorial substrate synthesis which tags each bead with a unique molecular record of its synthesis. 3· 4Beginning with l, 5b we removed the allyl protectinggroups ((Ph3P) 4Pd/dimedone) and alkylated (Bu4NF, THF) the re-maining part with the mesylate of the azo dye, disperse red, to yield the red-colored 2. Next we prepared an encoded substrate library of N-acylated tripeptides. The split synthesis method6 was used andresulted in a set of Merrifield beads havingonly
