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@ARTICLE{Hickman:15095,
author = {Hickman, D.T. and López-Deber, M.P. and Ndao, D.M. and
Silva, A.B. and Nand, D. and Pihlgren, M. and Giriens, V.
and Madani, R. and St.-Pierre, A. and Karastan, H. and
Nagel-Steger, L. and Willbold, D. and Riesner, D. and
Nicolau, C. and Baldus, M. and Pfeifer, A. and Muhs, A.},
title = {{S}equence-independent control of peptide conformation in
liposomal vaccines for targeting protein misfolding
diseases},
journal = {The journal of biological chemistry},
volume = {286},
issn = {0021-9258},
address = {Bethesda, Md.},
publisher = {Soc.},
reportid = {PreJuSER-15095},
pages = {13966 - 13976},
year = {2011},
note = {Solid-state NMR studies were supported by Netherlands
Organization for Scientific Research Grant 700.26.121. D.R.
is a member of the Board of Directors and Scientific
Advisory Board of AC Immune SA.},
abstract = {Synthetic peptide immunogens that mimic the conformation of
a target epitope of pathological relevance offer the
possibility to precisely control the immune response
specificity. Here, we performed conformational analyses
using a panel of peptides in order to investigate the key
parameters controlling their conformation upon integration
into liposomal bilayers. These revealed that the peptide
lipidation pattern, the lipid anchor chain length, and the
liposome surface charge all significantly alter peptide
conformation. Peptide aggregation could also be modulated
post-liposome assembly by the addition of distinct small
molecule β-sheet breakers. Immunization of both mice and
monkeys with a model liposomal vaccine containing β-sheet
aggregated lipopeptide (Palm1-15) induced polyclonal IgG
antibodies that specifically recognized β-sheet multimers
over monomer or non-pathological native protein. The
rational design of liposome-bound peptide immunogens with
defined conformation opens up the possibility to generate
vaccines against a range of protein misfolding diseases,
such as Alzheimer disease.},
keywords = {Alzheimer Disease: metabolism / Animals / Circular
Dichroism / Female / Humans / Immunoglobulin G: chemistry /
Liposomes: chemistry / Magnetic Resonance Spectroscopy /
Mice / Mice, Inbred C57BL / Peptides: chemistry / Protein
Conformation / Protein Folding / Protein Structure,
Secondary / Protein Structure, Tertiary / Proteostasis
Deficiencies: metabolism / Thiazoles: chemistry / Vaccines:
chemistry / Immunoglobulin G (NLM Chemicals) / Liposomes
(NLM Chemicals) / Peptides (NLM Chemicals) / Thiazoles (NLM
Chemicals) / Vaccines (NLM Chemicals) / thioflavin T (NLM
Chemicals) / J (WoSType)},
cin = {ICS-6},
ddc = {570},
cid = {I:(DE-Juel1)ICS-6-20110106},
pnm = {Funktion und Dysfunktion des Nervensystems / BioSoft:
Makromolekulare Systeme und biologische
Informationsverarbeitung},
pid = {G:(DE-Juel1)FUEK409 / G:(DE-Juel1)FUEK505},
shelfmark = {Biochemistry $\&$ Molecular Biology},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:21343310},
pmc = {pmc:PMC3077597},
UT = {WOS:000289556200019},
doi = {10.1074/jbc.M110.186338},
url = {https://juser.fz-juelich.de/record/15095},
}