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• W3046127638 endingPage "14471" @default.
• W3046127638 startingPage "14461" @default.
• W3046127638 abstract "Peptides and peptidomimetics represent the middle space between small molecules and large proteins—they retain the relatively small size and synthetic accessibility of small molecules while providing high binding specificity for biomolecular partners typically observed with proteins. During the course of our efforts to target intracellular protein–protein interactions in cancer, we observed that the cellular uptake of peptides is critically determined by the cell line—specifically, we noted that peptides show better uptake in cancer cells with enhanced macropinocytic indices. Here, we describe the results of our analysis of cellular penetration by different classes of conformationally stabilized peptides. We tested the uptake of linear peptides, peptide macrocycles, stabilized helices, β-hairpin peptides, and cross-linked helix dimers in 11 different cell lines. Efficient uptake of these conformationally defined constructs directly correlated with the macropinocytic activity of each cell line: high uptake of compounds was observed in cells with mutations in certain signaling pathways. Significantly, the study shows that constrained peptides follow the same uptake mechanism as proteins in macropinocytic cells, but unlike proteins, peptide mimics can be readily designed to resist denaturation and proteolytic degradation. Our findings expand the current understanding of cellular uptake in cancer cells by designed peptidomimetics and suggest that cancer cells with certain mutations are suitable mediums for the study of biological pathways with peptide leads." @default.
• W3046127638 created "2020-08-03" @default.
• W3046127638 creator A5003557201 @default.
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• W3046127638 creator A5064281189 @default.
• W3046127638 creator A5078028540 @default.
• W3046127638 date "2020-07-27" @default.
• W3046127638 modified "2023-10-17" @default.
• W3046127638 title "Macropinocytosis as a Key Determinant of Peptidomimetic Uptake in Cancer Cells" @default.
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• W3046127638 doi "https://doi.org/10.1021/jacs.0c02109" @default.
• W3046127638 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7755425" @default.
• W3046127638 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/32786217" @default.
• W3046127638 hasPublicationYear "2020" @default.
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