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- W3200714310 abstract "Biological membrane fusion is a highly specific and coordinated process as a multitude of vesicular fusion events proceed simultaneously in a complex environment with minimal off-target delivery. In this study, we develop a liposomal fusion model system with specific recognition using lipidated derivatives of a set of four de novo designed heterodimeric coiled coil (CC) peptide pairs. Content mixing was only obtained between liposomes functionalized with complementary peptides, demonstrating both fusogenic activity of CC peptides and the specificity of this model system. The diverse peptide fusogens revealed important relationships between the fusogenic efficacy and the peptide characteristics. The fusion efficiency increased from 20% to 70% as affinity between complementary peptides decreased, (from KF ≈ 108 to 104 M-1), and fusion efficiency also increased due to more pronounced asymmetric role-playing of membrane interacting 'K' peptides and homodimer-forming 'E' peptides. Furthermore, a new and highly fusogenic CC pair (E3/P1K) was discovered, providing an orthogonal peptide triad with the fusogenic CC pairs P2E/P2K and P3E/P3K. This E3/P1k pair was revealed, via molecular dynamics simulations, to have a shifted heptad repeat that can accommodate mismatched asparagine residues. These results will have broad implications not only for the fundamental understanding of CC design and how asparagine residues can be accommodated within the hydrophobic core, but also for drug delivery systems by revealing the necessary interplay of efficient peptide fusogens and enabling the targeted delivery of different carrier vesicles at various peptide-functionalized locations." @default.
- W3200714310 created "2021-09-27" @default.
- W3200714310 creator A5038669070 @default.
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- W3200714310 creator A5083596619 @default.
- W3200714310 date "2021-01-01" @default.
- W3200714310 modified "2023-10-18" @default.
- W3200714310 title "Liposome fusion with orthogonal coiled coil peptides as fusogens: the efficacy of roleplaying peptides" @default.
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- W3200714310 doi "https://doi.org/10.1039/d0sc06635d" @default.
- W3200714310 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/8549789" @default.
- W3200714310 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/34760163" @default.
- W3200714310 hasPublicationYear "2021" @default.
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