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231224s2013 xx |||||o 00| ||eng c |
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|a 10.1002/jcc.23213
|2 doi
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|a pubmed25n0746.xml
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|a DE-627
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|a eng
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|a Choi, Yoonjoo
|e verfasserin
|4 aut
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|a Structure-based redesign of proteins for minimal T-cell epitope content
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|c 2013
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|a Text
|b txt
|2 rdacontent
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|a ƒaComputermedien
|b c
|2 rdamedia
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|a ƒa Online-Ressource
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|2 rdacarrier
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|a Date Completed 02.07.2014
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|a Date Revised 23.03.2024
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|a published: Print-Electronic
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|a Citation Status MEDLINE
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|a Copyright © 2013 Wiley Periodicals, Inc.
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|a The protein universe displays a wealth of therapeutically relevant activities, but T-cell driven immune responses to non-"self" biological agents present a major impediment to harnessing the full diversity of these molecular functions. Mutagenic T-cell epitope deletion seeks to mitigate the immune response, but can typically address only a small number of epitopes. Here, we pursue a "bottom-up" approach that redesigns an entire protein to remain native-like but contain few if any immunogenic epitopes. We do so by extending the Rosetta flexible-backbone protein design software with an epitope scoring mechanism and appropriate constraints. The method is benchmarked with a diverse panel of proteins and applied to three targets of therapeutic interest. We show that the deimmunized designs indeed have minimal predicted epitope content and are native-like in terms of various quality measures, and moreover that they display levels of native sequence recovery comparable to those of non-deimmunized designs
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|a Journal Article
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|a Research Support, N.I.H., Extramural
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|a Epitopes, T-Lymphocyte
|2 NLM
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|a Proteins
|2 NLM
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1 |
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|a Griswold, Karl E
|e verfasserin
|4 aut
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1 |
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|a Bailey-Kellogg, Chris
|e verfasserin
|4 aut
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773 |
0 |
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|i Enthalten in
|t Journal of computational chemistry
|d 1984
|g 34(2013), 10 vom: 05. Apr., Seite 879-91
|w (DE-627)NLM098138448
|x 1096-987X
|7 nnns
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773 |
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|g volume:34
|g year:2013
|g number:10
|g day:05
|g month:04
|g pages:879-91
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|u http://dx.doi.org/10.1002/jcc.23213
|3 Volltext
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|d 34
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|h 879-91
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