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仿生亲和配基在蛋白质纯化中的应用。

Biomimetic Affinity Ligands for Protein Purification.

机构信息

iBB - Institute for Bioengineering and Biosciences, Instituto Superior Técnico, University of Lisbon, Lisbon, Portugal.

Department of Bioengineering, Instituto Superior Técnico, University of Lisbon, Lisbon, Portugal.

出版信息

Methods Mol Biol. 2021;2178:167-199. doi: 10.1007/978-1-0716-0775-6_14.

Abstract

The development of sophisticated molecular modeling software and new bioinformatic tools, as well as the emergence of data banks containing detailed information about a huge number of proteins, enabled the de novo intelligent design of synthetic affinity ligands. Such synthetic compounds can be tailored to mimic natural biological recognition motifs or to interact with key surface-exposed residues on target proteins, and are designated as "biomimetic ligands". A well-established methodology for generating biomimetic or synthetic affinity ligands integrates rational design with combinatorial solid-phase synthesis and screening, using the triazine scaffold and analogs of amino acid side chains to create molecular diversity.Triazine-based synthetic ligands are nontoxic, low-cost, and highly stable compounds that can replace advantageously natural biological ligands in the purification of proteins by affinity-based methodologies.

摘要

先进的分子建模软件和新的生物信息学工具的发展,以及包含大量蛋白质详细信息的数据银行的出现,使得从头开始智能设计合成亲和配体成为可能。这种合成化合物可以量身定制,以模拟天然的生物识别基序,或与靶蛋白表面暴露的关键残基相互作用,被称为“仿生配体”。一种成熟的生成仿生或合成亲和配体的方法是将合理设计与组合固相合成和筛选相结合,使用三嗪支架和氨基酸侧链类似物来创造分子多样性。基于三嗪的合成配体是无毒、低成本和高稳定性的化合物,可以在基于亲和性的蛋白质纯化方法中替代天然生物配体的优势。

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