Proteomic barcoding platform for macromolecular screening and delivery Journal Article
| Authors: | Wang, N.; McNeer, N. A.; Eton, E.; Fass, J.; Kentsis, A. |
| Article Title: | Proteomic barcoding platform for macromolecular screening and delivery |
| Abstract: | Engineered macromolecules offer compelling means for the therapy of conventionally undruggable interactions in human disease. However, their efficacy is limited by barriers to tissue and intracellular delivery. Inspired by recent advances in molecular barcoding and evolution, we developed BarcodeBabel, a generalized method for the design of libraries of peptide barcodes suitable for high-throughput mass spectrometry proteomics. Combined with PeptideBabel, a Monte Carlo sampling algorithm for the design of peptides with evolvable physicochemical properties and sequence complexity, we developed a barcoded library of cell penetrating peptides (CPPs) with distinct physicochemical features. Using quantitative targeted mass spectrometry, we identified CPPS with improved nuclear and cytoplasmic delivery exceeding hundreds of millions of molecules per human cell while maintaining minimal membrane disruption and negligible toxicity in vitro. These studies provide a proof of concept for peptide barcoding as a homogeneous high-throughput method for macromolecular screening and delivery. BarcodeBabel and PeptideBabel are available open-source from https://github.com/kentsisresearchgroup/. © 2024 American Chemical Society. |
| Keywords: | controlled study; human cell; mass spectrometry; ph; high throughput screening; high-throughput screening assays; algorithms; proteomics; chemistry; molecular evolution; algorithm; high performance liquid chromatography; room temperature; drug delivery system; desulfurization; peptide library; macromolecule; macromolecular substances; dna barcoding; procedures; cell-penetrating peptides; cell penetrating peptide; humans; human; article; hek293t cell line; kasumi-1 cell line; cell penetration; macromolecular drug delivery; mass spectrometry proteomics; molecular screening; peptide barcoding; huvec cell line |
| Journal Title: | Journal of Proteome Research |
| Volume: | 23 |
| Issue: | 6 |
| ISSN: | 1535-3893 |
| Publisher: | American Chemical Society |
| Date Published: | 2024-06-01 |
| Start Page: | 2067 |
| End Page: | 2077 |
| Language: | English |
| DOI: | 10.1021/acs.jproteome.4c00068 |
| PUBMED: | 38776430 |
| PROVIDER: | scopus |
| PMCID: | PMC11770985 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in PDF, misspelled as 'P30 CA08748'. Corresponding MSK author is Alex Kentsis -- Source: Scopus |
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