Selectide Technology: Bead-Binding Screening
Selectide Technology: Bead-Binding Screening
复制标题
Selectide 技术：珠子结合筛选
DOI：
--
复制
发表时间：
1994
期刊：
影响因子：
--
通讯作者：
M. Lebl
中科院分区：
文献类型：
--
作者：
K. Lam;M. Lebl
摘要选择肽法是一种基于单珠一肽(结构)概念的随机合成化学库方法。使用“分裂-合成”的方法来产生巨大的随机文库(106-108)。在合成结束时，每个珠子只表达一种化学实体(例如，肽)。然后同时测试整个文库是否与生物学上感兴趣的特定受体分子结合。然后分离出与受体分子特异相互作用的配体珠以进行结构测定。一旦鉴定出结合基序，就会产生二级文库(基于初级筛选的基序)，并在更严格的条件下进行筛选，以识别亲和力更高的线索。这一过程既适用于多肽文库，也适用于非多肽(小型有机)文库。在不可测序结构文库的情况下，必须应用编码原理来解释正反应小球的结构。与筛选结构平行合成编码肽，并使用经典的Edman降解(一步或多步)进行结构分析。为了排除大分子靶标(例如，受体、酶、抗体)与编码结构相互作用的可能性，开发了一种分离珠子表面(筛选结构)和内部(编码结构)的合成技术。这种一珠一结构的方法在铅识别的药物发现以及进一步优化初始引线方面具有非常重要的价值。它也是分子识别的重要研究工具。
Abstract The Selectide process is a random synthetic chemical library method based on the one-bead one-peptide (structure) concept. A "split-synthesis" method is used to generate huge random libraries (10 6 -10 8 ). At the end of the synthesis, each bead expresses only one chemical entity (e.g., peptide). The whole library is then tested simultaneously for binding to a specific acceptor molecule of biologic interest. The ligand bead that interacts specifically with the acceptor molecule is then isolated for structure determination. Once a binding motif is identified, a secondary library (based on the motif of the primary screen) is generated and screened under a more stringent condition to identify leads of higher affinity. This process can be applied to both peptide and nonpeptide (small organic) libraries. In the case of nonsequencable structure libraries, the coding principle has to be applied for structure elucidation of positively reacting beads. Coding peptide is synthesized in parallel to the screening structure, and classical Edman degradation (one or multiple-step) is used for structural analysis. To exclude the possibility of interaction of the macromolecular target (e.g., receptor, enzyme, antibody) with the coding structure, a synthetic technique for segregation of the surface (screening structure) and the interior (coding structure) of the beads was developed. The one-bead one-structure process is invaluable in drug discovery for lead identification as well as further optimization of the initial leads. It also serves as an important research tool for molecular recognition.