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Functionalization of Cobalt Porphyrin-Phospholipid Bilayers with His-tagged Ligands and Antigens

Methods to attach polypeptides to lipid bilayers are often indirect, ineffective and can represent a substantial bottleneck in the formation of functionalized lipid-based materials. Although the polyhistidine tag (his-tag) has been transformative in its simplicity and efficacy in binding to immobili...

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Autores principales: Shao, Shuai, Geng, Jumin, Yi, Hyun Ah, Gogia, Shobhit, Neelamegham, Sriram, Jacobs, Amy, Lovell, Jonathan F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4408904/
https://www.ncbi.nlm.nih.gov/pubmed/25901823
http://dx.doi.org/10.1038/nchem.2236
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author Shao, Shuai
Geng, Jumin
Yi, Hyun Ah
Gogia, Shobhit
Neelamegham, Sriram
Jacobs, Amy
Lovell, Jonathan F.
author_facet Shao, Shuai
Geng, Jumin
Yi, Hyun Ah
Gogia, Shobhit
Neelamegham, Sriram
Jacobs, Amy
Lovell, Jonathan F.
author_sort Shao, Shuai
collection PubMed
description Methods to attach polypeptides to lipid bilayers are often indirect, ineffective and can represent a substantial bottleneck in the formation of functionalized lipid-based materials. Although the polyhistidine tag (his-tag) has been transformative in its simplicity and efficacy in binding to immobilized metals, the successful application of this approach has been challenging in physiological settings. Here we show that lipid bilayers containing porphyin-phospholipid that is chelated with cobalt, but not other metals, can effectively capture his-tagged proteins and peptides. The binding follows a Co(II) to Co(III) transition and occurs within the sheltered hydrophobic bilayer, resulting in essentially irreversible attachment in serum or in million-fold excess of competing imidazole. Using this approach we anchored homing peptides into the bilayer of preformed and cargo-loaded liposomes to enable tumour-targeting without disrupting the bilayer integrity. As a further demonstration, a synthetic HIV-derived protein fragment was bound to immunogenic liposomes for potent antibody generation for an otherwise non-antigenic peptide.
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spelling pubmed-44089042015-11-01 Functionalization of Cobalt Porphyrin-Phospholipid Bilayers with His-tagged Ligands and Antigens Shao, Shuai Geng, Jumin Yi, Hyun Ah Gogia, Shobhit Neelamegham, Sriram Jacobs, Amy Lovell, Jonathan F. Nat Chem Article Methods to attach polypeptides to lipid bilayers are often indirect, ineffective and can represent a substantial bottleneck in the formation of functionalized lipid-based materials. Although the polyhistidine tag (his-tag) has been transformative in its simplicity and efficacy in binding to immobilized metals, the successful application of this approach has been challenging in physiological settings. Here we show that lipid bilayers containing porphyin-phospholipid that is chelated with cobalt, but not other metals, can effectively capture his-tagged proteins and peptides. The binding follows a Co(II) to Co(III) transition and occurs within the sheltered hydrophobic bilayer, resulting in essentially irreversible attachment in serum or in million-fold excess of competing imidazole. Using this approach we anchored homing peptides into the bilayer of preformed and cargo-loaded liposomes to enable tumour-targeting without disrupting the bilayer integrity. As a further demonstration, a synthetic HIV-derived protein fragment was bound to immunogenic liposomes for potent antibody generation for an otherwise non-antigenic peptide. 2015-04-20 2015-05 /pmc/articles/PMC4408904/ /pubmed/25901823 http://dx.doi.org/10.1038/nchem.2236 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Shao, Shuai
Geng, Jumin
Yi, Hyun Ah
Gogia, Shobhit
Neelamegham, Sriram
Jacobs, Amy
Lovell, Jonathan F.
Functionalization of Cobalt Porphyrin-Phospholipid Bilayers with His-tagged Ligands and Antigens
title Functionalization of Cobalt Porphyrin-Phospholipid Bilayers with His-tagged Ligands and Antigens
title_full Functionalization of Cobalt Porphyrin-Phospholipid Bilayers with His-tagged Ligands and Antigens
title_fullStr Functionalization of Cobalt Porphyrin-Phospholipid Bilayers with His-tagged Ligands and Antigens
title_full_unstemmed Functionalization of Cobalt Porphyrin-Phospholipid Bilayers with His-tagged Ligands and Antigens
title_short Functionalization of Cobalt Porphyrin-Phospholipid Bilayers with His-tagged Ligands and Antigens
title_sort functionalization of cobalt porphyrin-phospholipid bilayers with his-tagged ligands and antigens
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4408904/
https://www.ncbi.nlm.nih.gov/pubmed/25901823
http://dx.doi.org/10.1038/nchem.2236
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