Intracellular Target-Specific Accretion of Cell Penetrating Peptides and Bioportides: Ultrastructural and Biological Correlates

2.50
Hdl Handle:
http://hdl.handle.net/2436/621132
Title:
Intracellular Target-Specific Accretion of Cell Penetrating Peptides and Bioportides: Ultrastructural and Biological Correlates
Authors:
Jones, Sarah; Uusna, Julia; Langel, Ülo; Howl, John
Abstract:
Cell penetrating peptide (CPP) technologies provide a viable strategy to regulate the activities of intracellular proteins that may be intractable to other biological agents. In particular, the cationic helical domains of proteins have proven to be a reliable source of proteomimetic bioportides, CPPs that modulate the activities of intracellular proteins. In this study we have employed live cell imaging confocal microscopy to determine the precise intracellular distribution of a chemically diverse set of CPPs and bioportides. Our findings indicate that, following efficient cellular entry, peptides are usually accreted at intracellular sites rather than being freely maintained in an aqueous cytosolic environment. The binding of CPPs to proteins in a relatively stable manner provides a molecular explanation for our findings. By extension, it is probable that many bioportides influence biological processes through a dominant-negative influence upon discrete protein–protein interactions. As an example, we report that bioportides derived from the leucine-rich repeat kinase 2 discretely influence the biology and stability of this key therapeutic target in Parkinson’s disease. The intracellular site-specific accretion of CPPs and bioportides can also be readily modulated by the attachment of larger cargoes or, more conveniently, short homing motifs. We conclude that site-specific intracellular targeting could be further exploited to expand the scope of CPP technologies.
Citation:
Intracellular Target-Specific Accretion of Cell Penetrating Peptides and Bioportides: Ultrastructural and Biological Correlates
Publisher:
American Chemical Society
Journal:
Bioconjugate Chemistry
Issue Date:
14-Dec-2015
URI:
http://hdl.handle.net/2436/621132
DOI:
10.1021/acs.bioconjchem.5b00529
Additional Links:
http://pubs.acs.org/doi/10.1021/acs.bioconjchem.5b00529
Type:
Article
Language:
en
ISSN:
1043-1802; 1520-4812
Appears in Collections:
School of Biomedical Sciences and Physiology; School of Biomedical Sciences and Physiology

Full metadata record

DC FieldValue Language
dc.contributor.authorJones, Sarahen
dc.contributor.authorUusna, Juliaen
dc.contributor.authorLangel, Üloen
dc.contributor.authorHowl, Johnen
dc.date.accessioned2018-02-22T15:00:19Z-
dc.date.available2018-02-22T15:00:19Z-
dc.date.issued2015-12-14-
dc.identifier.citationIntracellular Target-Specific Accretion of Cell Penetrating Peptides and Bioportides: Ultrastructural and Biological Correlatesen
dc.identifier.issn1043-1802-
dc.identifier.issn1520-4812-
dc.identifier.doi10.1021/acs.bioconjchem.5b00529-
dc.identifier.urihttp://hdl.handle.net/2436/621132-
dc.description.abstractCell penetrating peptide (CPP) technologies provide a viable strategy to regulate the activities of intracellular proteins that may be intractable to other biological agents. In particular, the cationic helical domains of proteins have proven to be a reliable source of proteomimetic bioportides, CPPs that modulate the activities of intracellular proteins. In this study we have employed live cell imaging confocal microscopy to determine the precise intracellular distribution of a chemically diverse set of CPPs and bioportides. Our findings indicate that, following efficient cellular entry, peptides are usually accreted at intracellular sites rather than being freely maintained in an aqueous cytosolic environment. The binding of CPPs to proteins in a relatively stable manner provides a molecular explanation for our findings. By extension, it is probable that many bioportides influence biological processes through a dominant-negative influence upon discrete protein–protein interactions. As an example, we report that bioportides derived from the leucine-rich repeat kinase 2 discretely influence the biology and stability of this key therapeutic target in Parkinson’s disease. The intracellular site-specific accretion of CPPs and bioportides can also be readily modulated by the attachment of larger cargoes or, more conveniently, short homing motifs. We conclude that site-specific intracellular targeting could be further exploited to expand the scope of CPP technologies.en
dc.language.isoenen
dc.publisherAmerican Chemical Societyen
dc.relation.urlhttp://pubs.acs.org/doi/10.1021/acs.bioconjchem.5b00529en
dc.rightsArchived with thanks to Bioconjugate Chemistryen
dc.titleIntracellular Target-Specific Accretion of Cell Penetrating Peptides and Bioportides: Ultrastructural and Biological Correlatesen
dc.typeArticleen
dc.identifier.journalBioconjugate Chemistryen
dc.contributor.institutionResearch Institute in Healthcare Science, Faculty of Science and Engineering, University of Wolverhampton, Wulfruna Street, Wolverhampton, WV1 1LY, United Kingdom-
dc.contributor.institutionInstitute of Technology, University of Tartu, Nooruse 1, 50411, Tartu, Estonia-
dc.contributor.institutionInstitute of Technology, University of Tartu, Nooruse 1, 50411, Tartu, Estonia-
dc.contributor.institutionResearch Institute in Healthcare Science, Faculty of Science and Engineering, University of Wolverhampton, Wulfruna Street, Wolverhampton, WV1 1LY, United Kingdom-
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