Combinatorial Avidity Selection of Mosaic Landscape Phages Targeted at Breast Cancer Cells—An Alternative Mechanism of Directed Molecular Evolution
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 tr...
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doaj-59753f8b8fbe4703af04549d34c10e5a2020-11-24T21:27:03ZengMDPI AGViruses1999-49152019-08-0111978510.3390/v11090785v11090785Combinatorial Avidity Selection of Mosaic Landscape Phages Targeted at Breast Cancer Cells—An Alternative Mechanism of Directed Molecular EvolutionValery A. Petrenko0James W. Gillespie1Hai Xu2Tiffany O’Dell3Laura M. De Plano4Department of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, AL 36849, USADepartment of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, AL 36849, USADepartment of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, AL 36849, USADepartment of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, AL 36849, USADepartment of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, AL 36849, USALow 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.https://www.mdpi.com/1999-4915/11/9/785landscape phage displaydirected molecular evolutioncombinatorial selectionshort linear motifsdomain motif interactionbreast cancer |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Valery A. Petrenko James W. Gillespie Hai Xu Tiffany O’Dell Laura M. De Plano |
spellingShingle |
Valery A. Petrenko James W. Gillespie Hai Xu Tiffany O’Dell Laura M. De Plano Combinatorial Avidity Selection of Mosaic Landscape Phages Targeted at Breast Cancer Cells—An Alternative Mechanism of Directed Molecular Evolution Viruses landscape phage display directed molecular evolution combinatorial selection short linear motifs domain motif interaction breast cancer |
author_facet |
Valery A. Petrenko James W. Gillespie Hai Xu Tiffany O’Dell Laura M. De Plano |
author_sort |
Valery A. Petrenko |
title |
Combinatorial Avidity Selection of Mosaic Landscape Phages Targeted at Breast Cancer Cells—An Alternative Mechanism of Directed Molecular Evolution |
title_short |
Combinatorial Avidity Selection of Mosaic Landscape Phages Targeted at Breast Cancer Cells—An Alternative Mechanism of Directed Molecular Evolution |
title_full |
Combinatorial Avidity Selection of Mosaic Landscape Phages Targeted at Breast Cancer Cells—An Alternative Mechanism of Directed Molecular Evolution |
title_fullStr |
Combinatorial Avidity Selection of Mosaic Landscape Phages Targeted at Breast Cancer Cells—An Alternative Mechanism of Directed Molecular Evolution |
title_full_unstemmed |
Combinatorial Avidity Selection of Mosaic Landscape Phages Targeted at Breast Cancer Cells—An Alternative Mechanism of Directed Molecular Evolution |
title_sort |
combinatorial avidity selection of mosaic landscape phages targeted at breast cancer cells—an alternative mechanism of directed molecular evolution |
publisher |
MDPI AG |
series |
Viruses |
issn |
1999-4915 |
publishDate |
2019-08-01 |
description |
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. |
topic |
landscape phage display directed molecular evolution combinatorial selection short linear motifs domain motif interaction breast cancer |
url |
https://www.mdpi.com/1999-4915/11/9/785 |
work_keys_str_mv |
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