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Journal Article
Review
Emerging Methods and Design Principles for Cell-Penetrant Peptides.
Angewandte Chemie 2018 September 11
Biomolecules such as antibodies, proteins, and peptides are important tools for chemical biology and leads for drug development. They have been used to inhibit a variety of extracellular proteins, but accessing intracellular proteins has been much more challenging. In this review, we discuss diverse chemical approaches that have yielded cell-penetrant peptides and identify three distinct strategies: masking backbone amides, guanidinium group patterning, and amphipathic patterning. We summarize a growing number of large data sets, which are starting to reveal more specific design guidelines for each strategy. We also discuss advantages and disadvantages of current methods for quantifying cell penetration. Finally, we provide an overview of best-odds approaches for applying these new methods and design principles to optimize cytosolic penetration for a given bioactive peptide.
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