Department of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, AL 36849, USA.
National Veterinary Biological Medicine Engineering Research Center, Jiangsu Academy of Agricultural Sciences, Nanjing 210014, Jiangsu, China.
Viruses. 2019 Aug 26;11(9):785. doi: 10.3390/v11090785.
Low performance of actively targeted nanomedicines required revision of the traditional drug targeting paradigm and stimulated the development of novel phage-programmed, self-navigating drug delivery vehicles. In the proposed smart vehicles, targeting peptides, selected from phage libraries using traditional principles of affinity selection, are substituted for phage proteins discovered through combinatorial avidity selection. Here, we substantiate the potential of combinatorial avidity selection using landscape phage in the discovery of Short Linear Motifs (SLiMs) and their partner domains. We proved an algorithm for analysis of phage populations evolved through multistage screening of landscape phage libraries against the MDA-MB-231 breast cancer cell line. The suggested combinatorial avidity selection model proposes a multistage accumulation of Elementary Binding Units (EBU), or Core Motifs (CorMs), in landscape phage fusion peptides, serving as evolutionary initiators for formation of SLiMs. Combinatorial selection has the potential to harness directed molecular evolution to create novel smart materials with diverse novel, emergent properties.
主动靶向纳米药物的性能低下，需要修正传统的药物靶向范例，并刺激了新型噬菌体编程、自我导航药物输送载体的发展。在提出的智能载体中，靶向肽是使用传统亲和选择原则从噬菌体文库中选择的，替代了通过组合亲和力选择发现的噬菌体蛋白。在这里，我们通过组合亲和选择使用景观噬菌体来证实发现短线性基序 (SLiMs) 及其伴侣结构域的潜力。我们证明了一种分析通过针对 MDA-MB-231 乳腺癌细胞系的景观噬菌体文库进行多阶段筛选而进化的噬菌体群体的算法。所提出的组合亲和力选择模型提出了在景观噬菌体融合肽中积累 Elementary Binding Units (EBU) 或 Core Motifs (CorMs) 的多阶段过程，作为形成 SLiMs 的进化起点。组合选择有可能利用定向分子进化来创造具有各种新颖、新兴特性的新型智能材料。
