Conformation and Aggregation of Selectively PEGylated
and Lipidated Gastric Peptide Hormone Human PYY3–36
Version 2 2018-11-16, 19:33
Version 1 2018-10-03, 15:20
Posted on 2018-11-16 - 19:33
The
gastric peptide hormone human PYY3–36 is
a target for the development of therapeutics, especially for treatment
of obesity. The conformation and aggregation behavior of PEGylated
and lipidated derivatives of this peptide are examined using a combination
of fluorescence dye assays, circular dichroism (CD) spectroscopy,
analytical ultracentrifugation (AUC) measurements, small-angle X-ray
scattering (SAXS) and cryogenic-transmission electron microscopy (cryo-TEM).
The behavior of two PYY3–36 derivatives lipidated
(with octyl chains) in different positions is compared to that of
two derivatives with PEG attached at different residues and to that
of the native peptide. We find that, unexpectedly, PYY3–36 forms amyloid fibril structures above a critical aggregation concentration.
Formation of these structures is suppressed by PEGylation or lipidation.
PEGylation significantly reduces the (reversible) loss of α-helix
content observed on heating PYY3–36. The PEG conjugates
form mainly monomeric structures in solution- coiled-coil formation,
and other aggregation presumably being sterically hindered by swollen
PEG chains. However, some small aggregates are detected by AUC. In
complete contrast, both of the two lipidated peptides show the formation
of spherical micelle-like structures which are small oligomeric aggregates.
Our findings show that PEGylation and lipidation are complementary
strategies to tune the conformation and aggregation of the important
gastric peptide hormone human PYY3–36.
CITE THIS COLLECTION
DataCite
3 Biotech
3D Printing in Medicine
3D Research
3D-Printed Materials and Systems
4OR
AAPG Bulletin
AAPS Open
AAPS PharmSciTech
Abhandlungen aus dem Mathematischen Seminar der Universität Hamburg
ABI Technik (German)
Academic Medicine
Academic Pediatrics
Academic Psychiatry
Academic Questions
Academy of Management Discoveries
Academy of Management Journal
Academy of Management Learning and Education
Academy of Management Perspectives
Academy of Management Proceedings
Academy of Management Review
Castelletto, Valeria; Hamley, Ian W.; Seitsonen, Jani; Ruokolainen, Janne; Harris, Gemma; Bellmann-Sickert, Kathrin; et al. (2018). Conformation and Aggregation of Selectively PEGylated
and Lipidated Gastric Peptide Hormone Human PYY3–36. ACS Publications. Collection. https://doi.org/10.1021/acs.biomac.8b01209
or
Select your citation style and then place your mouse over the citation text to select it.
SHARE
Usage metrics
Read the peer-reviewed publication
AUTHORS (7)
VC
Valeria Castelletto
IH
Ian W. Hamley
JS
Jani Seitsonen
JR
Janne Ruokolainen
GH
Gemma Harris
KB
Kathrin Bellmann-Sickert
AB
Annette G. Beck-Sickinger