Discovery of biologically active peptides in random libraries: solution-phase testing after staged orthogonal release from resin beads.
Discovery of biologically active peptides in random libraries: solution-phase testing after staged orthogonal release from resin beads.
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在随机文库中发现生物活性肽：从树脂珠分阶段正交释放后进行溶液相测试。
DOI：
10.1073/pnas.90.24.11708
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发表时间：
1993
影响因子：
11.1
通讯作者：
Thorpe,D
中科院分区：
文献类型：
--
作者：
Salmon,SE;Lam,KS;Lebl,M;Kandola,A;Khattri,PS;Wade,S;Pátek,M;Kocis,P;Krchnák,V;Thorpe,D
为了加速药物发现，我们开发了一种方法，用于从包含数百万肽的文库中鉴定具有所需生物活性的单个肽。该方法使用化学合成的肽从不溶性珠中顺序正交释放，然后在溶液中进行测试。在该系统中，珠文库中的每个珠具有一个肽序列，但是肽分子用三种类型的化学接头连接到珠，包括在不同的最佳pH下可裂解的两种接头。不可切割的接头保持一些肽连接到珠上，用于对溶液测定的阳性进行测序。通过鉴定单克隆抗体和人血小板纤维蛋白原受体（糖蛋白IIb/IIIa）的配体，证明了这种发现技术的适用性。
To speed drug discovery, we developed an approach for identification of individual peptides with a desired biological activity from a library containing millions of peptides. The approach uses sequential orthogonal release of chemically synthesized peptides from insoluble beads, followed by testing in solution. In this system, each bead within a library of beads has one peptide sequence, but peptide molecules are attached to the bead with three types of chemical linkers, including two linkers cleavable at different pH optima. An uncleavable linker keeps some peptide attached to the bead for sequencing positives from the solution assay. Applicability of this discovery technique was documented by identifying ligands for a monoclonal antibody and for the human platelet fibrinogen receptor, glycoprotein IIb/IIIa.