Discovery of endosomalytic cell-penetrating peptides based on bacterial membrane-targeting sequences
Chuanjing An, Sheng Wei, Yuankun Dao, Xiaoya Wang, Weidong Dong, Xue You, Chao Tian, Zhili Zhang, Suwei Dong
Journal：BIOORGANIC CHEMISTRY
IF：5.1
DOI：10.1016/j.bioorg.2023.106424
PMID：36868126
Published：2023-02-15
research field：免疫学
Abstract
Cell-penetrating peptides (CPPs) are prominent scaffolds for drug developments and related research, particularly the endocytic delivery of biomacromolecules. Effective cargo release from endosomes prior to lysosomal degradation is a crucial step, where the rational design and selection of CPPs remains a challenge and calls for deeper mechanistic understandings. Here, we have investigated a strategy of designing CPPs that selectively disrupt endosomal membranes based on bacterial membrane targeting sequences (MTSs). Six synthesized MTS peptides all exhibit cell-penetrating abilities, among which two d -peptides ( d -EcMTS and d -TpMTS) are able to escape from endosomes and localize at ER after entering the cell. The utility of this strategy has been demonstrated by the intracellular delivery of green fluorescent protein (GFP). Together, these results suggest that the large pool of bacterial MTSs may be a rich source for the development of novel CPPs.
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