PEGylation site-dependent structural heterogeneity study of monoPEGylated human parathyroid hormone fragment hPTH(1-34)

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...

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Veröffentlicht in:Langmuir : the ACS journal of surfaces and colloids. - 1992. - 30(2014), 38 vom: 30. Sept., Seite 11421-7
1. Verfasser: Liu, Chih-Ying (VerfasserIn)
Weitere Verfasser: Li, Xin, Chen, Wen-Yih, Chang, Li-Chiao, Chen, Yi-Fan, Chen, Hsin-Lung, Sun, Ya-Sen, Lai, Hsiu-Yun, Huang, E-Wen
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2014
Zugriff auf das übergeordnete Werk:Langmuir : the ACS journal of surfaces and colloids
Schlagworte:Journal Article Research Support, Non-U.S. Gov't Teriparatide 10T9CSU89I Polyethylene Glycols 3WJQ0SDW1A
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520 |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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650 4 |a Research Support, Non-U.S. Gov't 
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650 7 |a Polyethylene Glycols  |2 NLM 
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700 1 |a Li, Xin  |e verfasserin  |4 aut 
700 1 |a Chen, Wen-Yih  |e verfasserin  |4 aut 
700 1 |a Chang, Li-Chiao  |e verfasserin  |4 aut 
700 1 |a Chen, Yi-Fan  |e verfasserin  |4 aut 
700 1 |a Chen, Hsin-Lung  |e verfasserin  |4 aut 
700 1 |a Sun, Ya-Sen  |e verfasserin  |4 aut 
700 1 |a Lai, Hsiu-Yun  |e verfasserin  |4 aut 
700 1 |a Huang, E-Wen  |e verfasserin  |4 aut 
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