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首页> 外文期刊>Combinatorial Chemistry & High Throughput Screening >Optimisation of a Peptide Library for Screening Specific RNA Ligands by Flow-Injection NMR
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Optimisation of a Peptide Library for Screening Specific RNA Ligands by Flow-Injection NMR

机译：通过流动注射NMR筛选特定RNA配体的肽库的优化

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摘要

Flow-injection NMR is a very attractive technique for identifying weak but specific ligandmacromolecule interactions. The low-sensitivity of this method is, however, a major concern which hinders its widespread application to large-scale screening. Focussing on RNA-targeting ligands, we have shown in this report that it is possible to design a peptide library that will simultaneously satisfy a number of physicochemical restraints and sample the sequence space in an “optimal” fashion. This library, which contains less than 200 peptides, covers most of the allowable tripeptide sequences in a non-redundant fashion. In addition, for almost any allowable tetrapeptide sequences, the library contains a close neighbor that will differ at the most by a single conservative replacement. A subset of this library was actually synthesised and used in a preliminary screen against human tRNALys3, the primer of HIV-1 reverse transcriptase.
机译：流动注射NMR是用于识别微弱但特定的配体-大分子相互作用的非常有吸引力的技术。然而，该方法的低灵敏度是主要关注点，这阻碍了其在大规模筛选中的广泛应用。着眼于靶向RNA的配体，我们在本报告中表明，可以设计一种肽库，该肽库将同时满足许多物理化学限制条件，并以“最佳”方式对序列空间进行采样。该文库包含少于200个肽，以非冗余方式涵盖了大多数允许的三肽序列。此外，对于几乎所有允许的四肽序列，该文库都包含一个紧密的邻居，该邻居之间的最大差异是单个保守替换。实际上已经合成了该文库的一个子集，并用于针对人类tRNALys3（HIV-1逆转录酶的引物）的初步筛选。

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