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Artificial Evolutionary Optimization Process to Improve the Functionality of Cell Penetrating Peptides.

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Crossing cellular membranes is a versatile molecular property that allows for a wide variety of peptides with cell penetrating capabilities. This broadness complicates identification of candidates suited best for a… Click to show full abstract

Crossing cellular membranes is a versatile molecular property that allows for a wide variety of peptides with cell penetrating capabilities. This broadness complicates identification of candidates suited best for a specific application. To facilitate the screening of this enormous molecular space in a supervised manner we here present a method to "breed" the desired molecules by applying the rules of Darwinian evolution. With this mate-and-check protocol, which combines an in silico evolution step with an in vitro performance test, cell penetrating peptides that are optimized for a specific task can be achieved in a few rounds of breeding. The procedure is simple and straightforward on the synthetic site but requires robust, highly reproducible and close-to-reality biological assays to yield realistic functional output. With this technology even top-performing peptides can be further improved and functionally adjusted.

Keywords: penetrating peptides; artificial evolutionary; optimization process; cell penetrating; evolutionary optimization

Journal Title: Methods in molecular biology
Year Published: 2022

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