CUED Publications database

Controlling the bioactivity of a peptide hormone in vivo by reversible self-assembly

Ouberai, MM and Dos Santos, ALG and Kinna, S and Madalli, S and Hornigold, DC and Baker, D and Naylor, J and Sheldrake, L and Corkill, DJ and Hood, J and Vicini, P and Uddin, S and Bishop, S and Varley, PG and Welland, ME (2017) Controlling the bioactivity of a peptide hormone in vivo by reversible self-assembly. Nature Communications, 8. 1026-.

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Abstract

The use of peptides as therapeutic agents is undergoing a renaissance with the expectation of new drugs with enhanced levels of efficacy and safety. Their clinical potential will be only fully realised once their physicochemical and pharmacokinetic properties have been precisely controlled. Here we demonstrate a reversible peptide self-assembly strategy to control and prolong the bioactivity of a native peptide hormone in vivo. We show that oxyntomodulin, a peptide with potential to treat obesity and diabetes, self-assembles into a stable nanofibril formulation which subsequently dissociates to release active peptide and produces a pharmacological effect in vivo. The subcutaneous administration of the nanofibrils in rats results in greatly prolonged exposure, with a constant oxyntomodulin bioactivity detectable in serum for at least 5 days as compared to free oxyntomodulin which is undetectable after only 4 h. Such an approach is simple, cost-efficient and generic in addressing the limitations of peptide therapeutics.

Item Type: Article
Uncontrolled Keywords: Animals Glucose Injections, Subcutaneous Male Mice Mice, Inbred C57BL Obesity Oxyntomodulin Peptide Hormones Rats Rats, Sprague-Dawley
Subjects: UNSPECIFIED
Divisions: Div B > Solid State Electronics and Nanoscale Science
Depositing User: Cron Job
Date Deposited: 26 Oct 2017 01:26
Last Modified: 10 Apr 2021 22:24
DOI: 10.1038/s41467-017-01114-1