Haußner Christina, Lach Johannes, Eichler Jutta
Department of Chemistry and Pharmacy, University of Erlangen-Nurnberg, Schuhstr. 19, 91052 Erlangen, Germany.
Department of Chemistry and Pharmacy, University of Erlangen-Nurnberg, Schuhstr. 19, 91052 Erlangen, Germany.
Curr Opin Chem Biol. 2017 Oct;40:72-77. doi: 10.1016/j.cbpa.2017.07.001. Epub 2017 Sep 18.
The rational/structure-based design and/or combinatorial development of molecules capable of selectively binding to a protein, represents a promising strategy for a range of biomedical applications, in particular the inhibition of disease-associated protein-ligand interactions. The design of such protein binding molecules is often based on an antibody against the target protein, or involves the generation of smaller molecules that retain the binding characteristics of the antibody. Alternatively, protein binding molecules can be selected from protein libraries based on small, stably folded protein scaffolds presenting flexible loops, which are randomized in the libraries. In addition to recombinantly synthesized molecules, synthetic antibody paratope mimetic peptides have emerged as promising molecules for the design of antibody mimics.
能够选择性结合蛋白质的分子的基于理性/结构的设计和/或组合开发,代表了一系列生物医学应用的一种有前景的策略,特别是对疾病相关蛋白质-配体相互作用的抑制。此类蛋白质结合分子的设计通常基于针对靶蛋白的抗体,或涉及生成保留抗体结合特性的小分子。另外,蛋白质结合分子可基于呈现柔性环的小的、稳定折叠的蛋白质支架从蛋白质文库中选择,这些柔性环在文库中是随机化的。除了重组合成分子外,合成抗体互补位模拟肽已成为设计抗体模拟物的有前景的分子。