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Co-assembly of liposomes, Dendrimersomes, and Polymersomes with amphiphilic Janus dendrimers conjugated to Mono- and Tris-Nitrilotriacetic Acid (NTA, TrisNTA) enhances protein recruitment
; Rivera-Martinez, Naomi ; Raab, Calvin J. ; Bermudez, Jessica G. ; Good, Matthew C. ; ; Percec, Virgil
Rivera-Martinez, Naomi
Raab, Calvin J.
Bermudez, Jessica G.
Good, Matthew C.
Percec, Virgil
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Journal article
Date
2021-12-30
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Chemistry
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http://dx.doi.org/10.1016/j.giant.2021.100089
Abstract
Metal-chelating ligands such as nitrilotriacetic acid (NTA) bind to polyhistidine-tagged (His-tagged) proteins. Lipids conjugated to NTA are widely used to decorate the surface of liposomes with proteins in cell biology applications. Multivalent NTA ligands such as tris-nitrilotriacetic acid (TrisNTA) display higher affinities than the monovalent NTA when co-assembled with phospholipids and cholesterol in liposomes. However, there is a limited number of available lipids conjugated to NTA and only few are commercially available. Additionally, their activity diminishes during storage or upon exposure to air. Here we report a library of five amphiphilic Janus dendrimers conjugated to NTA (JD-NTA) and three to TrisNTA (JD-TrisNTA). Both JD-NTA and JD-TrisNTA are indefinitely stable at room temperature in air and preliminary results demonstrate that they co-assemble with phospholipids and cholesterol into liposomes, with Janus dendrimers into dendrimersomes, and with block copolymers into polymersomes. The resulting hybrid liposomes co-assembled with JD-NTA display up to thirty-fold higher activity towards His-tagged fluorescent proteins when compared to lipid-NTAs. Hybrid liposomes co-assembled with JD-TrisNTA exhibit even higher binding affinity to His-tagged proteins and can function at much lower ligand concentration in hybrid liposomes than those containing JD-NTA. These preliminary results demonstrate the power of modular synthesis of JD-NTA or JD-TrisNTA to provide highly efficient new tools for biological reconstitution and synthetic cell biology as well as for nanomedicine.
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Qi Xiao, Naomi Rivera-Martinez, Calvin J. Raab, Jessica G. Bermudez, Matthew C. Good, Michael L. Klein, Virgil Percec, Co-assembly of liposomes, Dendrimersomes, and Polymersomes with amphiphilic Janus dendrimers conjugated to Mono- and Tris-Nitrilotriacetic Acid (NTA, TrisNTA) enhances protein recruitment, Giant, Volume 9, 2022, 100089, ISSN 2666-5425, https://doi.org/10.1016/j.giant.2021.100089.
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Elsevier
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Giant, Vol. 9
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