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首页> 外文期刊>Life sciences >Application of 'one-bead one-compound' combinatorial library methods in signal transduction research.
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Application of 'one-bead one-compound' combinatorial library methods in signal transduction research.

机译：“单珠一化合物”组合文库方法在信号转导研究中的应用。

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摘要

Using a "split-synthesis" solid phase synthetic approach, bead libraries can be generated such that each bead displays only one chemical entity. This "one-bead one-compound" combinatorial library can then be assayed for specific biological properties using either a solid-phase on-bead binding or functional assay, or a releasable solution phase assay. Positive compound-beads can then be isolated for structure determination. Various assay systems to screen such a "one-bead one-compound" library are described. We have used this combinatorial library method to discover peptides that bind to the cell surface immunoglobulins of murine lymphoma cells. Such peptides, when presented in an oligomeric form to a lymphoma cell are able to induce signal transduction. Additionally, we have also applied the "one-bead one-compound" combinatory library approach to elucidate peptide substrate motifs for protein tyrosine kinases. Multiple distinct peptide motifs were identified for p60(c-src) protein tyrosine kinase. Using the identified peptide substrates as templates, potent and highly specific pseudosubstrate-based peptide inhibitors were developed.
机译：使用“分裂合成”固相合成方法，可以生成珠子库，使得每个珠子仅显示一个化学实体。然后可以使用固相珠上结合或功能测定或可释放溶液相测定来测定该“单珠单化合物”组合文库的特定生物学特性。然后可以分离出阳性化合物珠子用于结构测定。描述了用于筛选这种“单珠单化合物”文库的各种测定系统。我们已经使用了这种组合文库方法来发现与鼠淋巴瘤细胞的细胞表面免疫球蛋白结合的肽。当这些肽以寡聚形式存在于淋巴瘤细胞时，它们能够诱导信号转导。此外，我们还应用了“单珠单化合物”组合文库方法来阐明蛋白酪氨酸激酶的肽底物基序。为p60（c-src）蛋白酪氨酸激酶鉴定了多个不同的肽基序。使用鉴定出的肽底物作为模板，开发了有效且高度特异性的基于伪底物的肽抑制剂。

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