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231224s2014 xx |||||o 00| ||eng c |
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|a 10.1021/la501689d
|2 doi
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|a pubmed24n0804.xml
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|a DE-627
|b ger
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|e rakwb
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|a eng
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|a Liu, Chih-Ying
|e verfasserin
|4 aut
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|a PEGylation site-dependent structural heterogeneity study of monoPEGylated human parathyroid hormone fragment hPTH(1-34)
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|c 2014
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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 02.07.2015
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|a Date Revised 02.12.2018
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|a published: Print-Electronic
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|a Citation Status MEDLINE
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|a The structures of C- and N-terminally monoPEGylated human parathyroid hormone fragment hPTH(1-34) as well as their unmodified counterparts, poly(ethylene glycol) (PEG) and hPTH(1-34), have been studied by small-angle neutron scattering (SANS). The scattering results show that free hPTH(1-34) in 100 mM phosphate buffer (pH 7.4) aggregates into clusters. After conjugation with PEG, the PEG-peptide conjugates self-assemble into a supramolecular core-shell structure with a cylindrical shape. The PEG chains form a shell around the hPTH(1-34) core to shield hPTH(1-34) from the solvent. The detailed structural information on the self-assembled structures is extracted from SANS using a model of the cylindrical core with a shell of Gaussian chains attached to the core surface. On the basis of the data, because of the charge-dipole interactions between the conjugated PEG chain and the peptide, the conjugated PEG chain forms a more collapsed conformation compared to free PEG. Moreover, the size of the self-assembled structures formed by the C-terminally monoPEGylated hPTH(1-34) is about 3 times larger than that of the N-terminally monoPEGylated hPTH(1-34). The different aggregation numbers of the self-assembled structures, triggered by different PEGylation sites, are reported. These size discrepancies because of different PEGylation sites could potentially affect the pharmacokinetics of the hPTH(1-34) drug
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|a Journal Article
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|a Research Support, Non-U.S. Gov't
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|a Teriparatide
|2 NLM
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|a 10T9CSU89I
|2 NLM
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|a Polyethylene Glycols
|2 NLM
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|a 3WJQ0SDW1A
|2 NLM
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|a Li, Xin
|e verfasserin
|4 aut
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|a Chen, Wen-Yih
|e verfasserin
|4 aut
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|a Chang, Li-Chiao
|e verfasserin
|4 aut
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|a Chen, Yi-Fan
|e verfasserin
|4 aut
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|a Chen, Hsin-Lung
|e verfasserin
|4 aut
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|a Sun, Ya-Sen
|e verfasserin
|4 aut
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|a Lai, Hsiu-Yun
|e verfasserin
|4 aut
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|a Huang, E-Wen
|e verfasserin
|4 aut
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|i Enthalten in
|t Langmuir : the ACS journal of surfaces and colloids
|d 1992
|g 30(2014), 38 vom: 30. Sept., Seite 11421-7
|w (DE-627)NLM098181009
|x 1520-5827
|7 nnns
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|g volume:30
|g year:2014
|g number:38
|g day:30
|g month:09
|g pages:11421-7
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|u http://dx.doi.org/10.1021/la501689d
|3 Volltext
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