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Combinatorial Avidity Selection of Mosaic Landscape Phages Targeted at Breast Cancer Cells-An Alternative Mechanism of Directed Molecular Evolution

文献类型: 外文期刊

作者: Petrenko, Valery A. 1 ; Gillespie, James W. 1 ; Xu, Hai 1 ; O'Dell, Tiffany 1 ; De Plano, Laura M. 1 ;

作者机构: 1.Auburn Univ, Coll Vet, Dept Pathobiol, Auburn, AL 36849 USA

2.Jiangsu Acad Agr Sci, Natl Vet Biol Med Engn Res Ctr, Nanjing 210014, Jiangsu, Peoples R China

3.Univ Messina, Dept Chem Sci Biol Pharmaceut & Environm, Viale F Stagno dAlcontres 31, I-98166 Messina, Italy

关键词: landscape phage display; directed molecular evolution; combinatorial selection; short linear motifs; domain motif interaction; breast cancer

期刊名称:VIRUSES-BASEL ( 影响因子:5.048; 五年影响因子:5.127 )

ISSN:

年卷期: 2019 年 11 卷 9 期

页码:

收录情况: SCI

摘要: 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.

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