Sousa Isabel T, Taipa M Angela
Centre for Biological and Chemical Engineering, Institute for Biotechnology and Bioengineering (IBB), Instituto Superior Técnico, Technical University of Lisbon, Lisbon, Portugal.
Methods Mol Biol. 2014;1129:231-62. doi: 10.1007/978-1-62703-977-2_20.
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 analogues of amino acids side chains to create molecular diversity.Triazine-based synthetic ligands are nontoxic, low-cost, highly stable compounds that can replace advantageously natural biological ligands in the purification of proteins by affinity-based methodologies.
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库的出现,使得合成亲和配体的从头智能设计成为可能。这类合成化合物可以进行定制,以模拟天然生物识别基序,或与目标蛋白质表面关键的暴露残基相互作用,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及筛选相结合,利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、高度稳定的化合物,在基于亲和方法的蛋白质纯化中,能够有利地替代天然生物配体。