The Effect of Lipidation on the Self-Assembly of the Gut-Derived Peptide Hormone PYY3-36

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The Effect of Lipidation on the Self-Assembly of the Gut-Derived Peptide Hormone PYY3-36. / Hutchinson, Jessica A.; Burholt, Samuel; Hamley, Ian W.; Lundback, Anna-Karin; Uddin, Shahid; dos Santos, Ana Gomes; Reza, Mehedi; Seitsonen, Jani; Ruokolainen, Janne.

In: BIOCONJUGATE CHEMISTRY, Vol. 29, No. 7, 07.2018, p. 2296-2308.

Research output: Contribution to journalArticleScientificpeer-review

Harvard

Hutchinson, JA, Burholt, S, Hamley, IW, Lundback, A-K, Uddin, S, dos Santos, AG, Reza, M, Seitsonen, J & Ruokolainen, J 2018, 'The Effect of Lipidation on the Self-Assembly of the Gut-Derived Peptide Hormone PYY3-36' BIOCONJUGATE CHEMISTRY, vol. 29, no. 7, pp. 2296-2308. https://doi.org/10.1021/acs.bioconjchem.8b00286

APA

Hutchinson, J. A., Burholt, S., Hamley, I. W., Lundback, A-K., Uddin, S., dos Santos, A. G., ... Ruokolainen, J. (2018). The Effect of Lipidation on the Self-Assembly of the Gut-Derived Peptide Hormone PYY3-36. BIOCONJUGATE CHEMISTRY, 29(7), 2296-2308. https://doi.org/10.1021/acs.bioconjchem.8b00286

Vancouver

Hutchinson JA, Burholt S, Hamley IW, Lundback A-K, Uddin S, dos Santos AG et al. The Effect of Lipidation on the Self-Assembly of the Gut-Derived Peptide Hormone PYY3-36. BIOCONJUGATE CHEMISTRY. 2018 Jul;29(7):2296-2308. https://doi.org/10.1021/acs.bioconjchem.8b00286

Author

Hutchinson, Jessica A. ; Burholt, Samuel ; Hamley, Ian W. ; Lundback, Anna-Karin ; Uddin, Shahid ; dos Santos, Ana Gomes ; Reza, Mehedi ; Seitsonen, Jani ; Ruokolainen, Janne. / The Effect of Lipidation on the Self-Assembly of the Gut-Derived Peptide Hormone PYY3-36. In: BIOCONJUGATE CHEMISTRY. 2018 ; Vol. 29, No. 7. pp. 2296-2308.

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@article{21bf7ede06a6413080b792dbedafb2a8,
title = "The Effect of Lipidation on the Self-Assembly of the Gut-Derived Peptide Hormone PYY3-36",
abstract = "Lipidation is a powerful strategy to improve the stability in vivo of peptide drugs. Attachment of a lipid chain to a hydrophilic peptide leads to amphiphilicity and the potential for surfactant-like self-assembly. Here, the self-assembly and conformation of three lipidated derivatives of the gastrointestinal peptide hormone PYY3-36 is examined using a comprehensive range of spectroscopic, scattering, and electron microscopy methods and compared to those of the parent PYY3-36 peptide. The peptides are lipidated at Ser(11), Arg(17), or Arg(23) in the peptide; the former is within the beta-turn domain (based on the published solution NMR structure), and the latter two are both within the alpha-helical domain. We show that it is possible to access a remarkable diversity of nanostructures ranging from micelles to nanotapes and fibrillar hydrogels by control of assembly conditions (concentration, pH, and temperature). All of the lipopeptides self-assemble above a critical aggregation concentration (cac), determined through pyrene fluorescence probe measurements, and they all have predominantly alpha-helical secondary structure at their native pH. The pH and temperature dependence of the alpha-helical conformation were probed via circular dichroism spectroscopy experiments. Lipidation was found to provide enhanced stability against changes in temperature and pH. The self-assembled structures were investigated using small-angle X-ray scattering (SAXS) and cryogenic transmission electron microscopy (cryo-TEM). Distinct differences in nanostructure were observed for lipidated and unlipidated peptides, also depending on the position of lipidation. Remarkably, micelles containing lipopeptides with alpha-helical peptide conformation were observed. Gelation was observed at higher concentrations in certain pH intervals for the lipidated peptides, but not for unlipidated PYY3-36. Thus, lipidation, in addition to enhancing stability against pH and temperature variation, also provides a route to prepare PYY peptide hydrogels. These findings provide important insights into the control of PYY3-36 conformation and aggregation by lipidation, relevant to the development of future therapeutics based on this peptide hormone, for example, in treatments for obesity.",
keywords = "GLUCAGON-LIKE PEPTIDE-1, HUMAN PANCREATIC-POLYPEPTIDE, AMPHIPHILE NANOFIBERS, FOOD-INTAKE, APPETITE CONTROL, PP-FOLD, YY, RECEPTOR, PYY, PROTEIN",
author = "Hutchinson, {Jessica A.} and Samuel Burholt and Hamley, {Ian W.} and Anna-Karin Lundback and Shahid Uddin and {dos Santos}, {Ana Gomes} and Mehedi Reza and Jani Seitsonen and Janne Ruokolainen",
year = "2018",
month = "7",
doi = "10.1021/acs.bioconjchem.8b00286",
language = "English",
volume = "29",
pages = "2296--2308",
journal = "BIOCONJUGATE CHEMISTRY",
issn = "1043-1802",
publisher = "AMERICAN CHEMICAL SOCIETY",
number = "7",

}

RIS - Download

TY - JOUR

T1 - The Effect of Lipidation on the Self-Assembly of the Gut-Derived Peptide Hormone PYY3-36

AU - Hutchinson, Jessica A.

AU - Burholt, Samuel

AU - Hamley, Ian W.

AU - Lundback, Anna-Karin

AU - Uddin, Shahid

AU - dos Santos, Ana Gomes

AU - Reza, Mehedi

AU - Seitsonen, Jani

AU - Ruokolainen, Janne

PY - 2018/7

Y1 - 2018/7

N2 - Lipidation is a powerful strategy to improve the stability in vivo of peptide drugs. Attachment of a lipid chain to a hydrophilic peptide leads to amphiphilicity and the potential for surfactant-like self-assembly. Here, the self-assembly and conformation of three lipidated derivatives of the gastrointestinal peptide hormone PYY3-36 is examined using a comprehensive range of spectroscopic, scattering, and electron microscopy methods and compared to those of the parent PYY3-36 peptide. The peptides are lipidated at Ser(11), Arg(17), or Arg(23) in the peptide; the former is within the beta-turn domain (based on the published solution NMR structure), and the latter two are both within the alpha-helical domain. We show that it is possible to access a remarkable diversity of nanostructures ranging from micelles to nanotapes and fibrillar hydrogels by control of assembly conditions (concentration, pH, and temperature). All of the lipopeptides self-assemble above a critical aggregation concentration (cac), determined through pyrene fluorescence probe measurements, and they all have predominantly alpha-helical secondary structure at their native pH. The pH and temperature dependence of the alpha-helical conformation were probed via circular dichroism spectroscopy experiments. Lipidation was found to provide enhanced stability against changes in temperature and pH. The self-assembled structures were investigated using small-angle X-ray scattering (SAXS) and cryogenic transmission electron microscopy (cryo-TEM). Distinct differences in nanostructure were observed for lipidated and unlipidated peptides, also depending on the position of lipidation. Remarkably, micelles containing lipopeptides with alpha-helical peptide conformation were observed. Gelation was observed at higher concentrations in certain pH intervals for the lipidated peptides, but not for unlipidated PYY3-36. Thus, lipidation, in addition to enhancing stability against pH and temperature variation, also provides a route to prepare PYY peptide hydrogels. These findings provide important insights into the control of PYY3-36 conformation and aggregation by lipidation, relevant to the development of future therapeutics based on this peptide hormone, for example, in treatments for obesity.

AB - Lipidation is a powerful strategy to improve the stability in vivo of peptide drugs. Attachment of a lipid chain to a hydrophilic peptide leads to amphiphilicity and the potential for surfactant-like self-assembly. Here, the self-assembly and conformation of three lipidated derivatives of the gastrointestinal peptide hormone PYY3-36 is examined using a comprehensive range of spectroscopic, scattering, and electron microscopy methods and compared to those of the parent PYY3-36 peptide. The peptides are lipidated at Ser(11), Arg(17), or Arg(23) in the peptide; the former is within the beta-turn domain (based on the published solution NMR structure), and the latter two are both within the alpha-helical domain. We show that it is possible to access a remarkable diversity of nanostructures ranging from micelles to nanotapes and fibrillar hydrogels by control of assembly conditions (concentration, pH, and temperature). All of the lipopeptides self-assemble above a critical aggregation concentration (cac), determined through pyrene fluorescence probe measurements, and they all have predominantly alpha-helical secondary structure at their native pH. The pH and temperature dependence of the alpha-helical conformation were probed via circular dichroism spectroscopy experiments. Lipidation was found to provide enhanced stability against changes in temperature and pH. The self-assembled structures were investigated using small-angle X-ray scattering (SAXS) and cryogenic transmission electron microscopy (cryo-TEM). Distinct differences in nanostructure were observed for lipidated and unlipidated peptides, also depending on the position of lipidation. Remarkably, micelles containing lipopeptides with alpha-helical peptide conformation were observed. Gelation was observed at higher concentrations in certain pH intervals for the lipidated peptides, but not for unlipidated PYY3-36. Thus, lipidation, in addition to enhancing stability against pH and temperature variation, also provides a route to prepare PYY peptide hydrogels. These findings provide important insights into the control of PYY3-36 conformation and aggregation by lipidation, relevant to the development of future therapeutics based on this peptide hormone, for example, in treatments for obesity.

KW - GLUCAGON-LIKE PEPTIDE-1

KW - HUMAN PANCREATIC-POLYPEPTIDE

KW - AMPHIPHILE NANOFIBERS

KW - FOOD-INTAKE

KW - APPETITE CONTROL

KW - PP-FOLD

KW - YY

KW - RECEPTOR

KW - PYY

KW - PROTEIN

U2 - 10.1021/acs.bioconjchem.8b00286

DO - 10.1021/acs.bioconjchem.8b00286

M3 - Article

VL - 29

SP - 2296

EP - 2308

JO - BIOCONJUGATE CHEMISTRY

JF - BIOCONJUGATE CHEMISTRY

SN - 1043-1802

IS - 7

ER -

ID: 27449333