1 research outputs found
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,
polyÂ(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 hPTHÂ(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 hPTHÂ(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