Cyclization enhances function of linear anti-arthritic peptides

This study describes the biophysical and immunomodulatory features of a cyclic peptide termed C1 which consists of alternating d-, l-amino acids and is capable of inhibiting IL-2 production in vitro and reducing the induction and extent of T-cell mediated inflammation in animal models. Solid-state n...

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Main Authors: Ali, Marina, Amon, Michael, Bender, Vera, Bolte, Andrea, Separovic, Frances, Benson, Heather, Manolios, Nicholas
Format: Journal Article
Published: Academic Press 2014
Subjects:
Online Access:http://hdl.handle.net/20.500.11937/23307
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author Ali, Marina
Amon, Michael
Bender, Vera
Bolte, Andrea
Separovic, Frances
Benson, Heather
Manolios, Nicholas
author_facet Ali, Marina
Amon, Michael
Bender, Vera
Bolte, Andrea
Separovic, Frances
Benson, Heather
Manolios, Nicholas
author_sort Ali, Marina
building Curtin Institutional Repository
collection Online Access
description This study describes the biophysical and immunomodulatory features of a cyclic peptide termed C1 which consists of alternating d-, l-amino acids and is capable of inhibiting IL-2 production in vitro and reducing the induction and extent of T-cell mediated inflammation in animal models. Solid-state nuclear magnetic resonance demonstrates that the peptide orders the lipid bilayer, suggesting a transmembrane orientation, and this is supported by surface plasmon resonance indicating strong binding affinity of C1 to model membranes. In vitro cell viability and proliferation assays show that C1 does not disrupt the integrity of cell surface membranes. Permeation studies of C1 and analogs across human epidermis cells show that the stability and skin permeability are enhanced by cyclization. Treatment with C1 in an asthma and in an arthritis animal model resulted in a suppressed immune response. Cyclization may be a useful means of enhancing biological linear peptide activity and improving delivery.
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institution Curtin University Malaysia
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publishDate 2014
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spelling curtin-20.500.11937-233072017-09-13T15:58:25Z Cyclization enhances function of linear anti-arthritic peptides Ali, Marina Amon, Michael Bender, Vera Bolte, Andrea Separovic, Frances Benson, Heather Manolios, Nicholas Arthritis T cells Asthma Peptides NMR Inflammation This study describes the biophysical and immunomodulatory features of a cyclic peptide termed C1 which consists of alternating d-, l-amino acids and is capable of inhibiting IL-2 production in vitro and reducing the induction and extent of T-cell mediated inflammation in animal models. Solid-state nuclear magnetic resonance demonstrates that the peptide orders the lipid bilayer, suggesting a transmembrane orientation, and this is supported by surface plasmon resonance indicating strong binding affinity of C1 to model membranes. In vitro cell viability and proliferation assays show that C1 does not disrupt the integrity of cell surface membranes. Permeation studies of C1 and analogs across human epidermis cells show that the stability and skin permeability are enhanced by cyclization. Treatment with C1 in an asthma and in an arthritis animal model resulted in a suppressed immune response. Cyclization may be a useful means of enhancing biological linear peptide activity and improving delivery. 2014 Journal Article http://hdl.handle.net/20.500.11937/23307 10.1016/j.clim.2013.10.005 Academic Press restricted
spellingShingle Arthritis
T cells
Asthma
Peptides
NMR
Inflammation
Ali, Marina
Amon, Michael
Bender, Vera
Bolte, Andrea
Separovic, Frances
Benson, Heather
Manolios, Nicholas
Cyclization enhances function of linear anti-arthritic peptides
title Cyclization enhances function of linear anti-arthritic peptides
title_full Cyclization enhances function of linear anti-arthritic peptides
title_fullStr Cyclization enhances function of linear anti-arthritic peptides
title_full_unstemmed Cyclization enhances function of linear anti-arthritic peptides
title_short Cyclization enhances function of linear anti-arthritic peptides
title_sort cyclization enhances function of linear anti-arthritic peptides
topic Arthritis
T cells
Asthma
Peptides
NMR
Inflammation
url http://hdl.handle.net/20.500.11937/23307