
==== Front
bioRxiv
BIORXIV
bioRxiv
2692-8205
Cold Spring Harbor Laboratory

10.1101/2024.08.22.609257
preprint
1
Article
In vivo Antibody Painting for Next Generation Weight Loss Drugs
Kitahara Katsushi
Rondon Aurélie
Miller Edward
Mak Howard H.
Loas Andrei
Pentelute Bradley L.
23 8 2024
2024.08.22.609257https://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator.
http://biorxiv.org/lookup/doi/10.1101/2024.08.22.609257
nihpp-2024.08.22.609257.pdf
Abstract

Peptide-based therapeutics are currently in great demand but often suffer from rapid clearance and accumulation in off-target tissues which continue to present barriers in their clinical translation. Here, we developed an electrophilic peptide for the attachment of therapeutics to native immunoglobulin (IgG) in vivo, enabling the bioorthogonal covalent linkage, or ‘painting’, of peptide drugs of choice to circulating IgGs directly in live animals. Native IgG painting with glucagon-like peptide-1 (GLP-1) results in sustained body weight loss and prolonged blood glucose management after one dose. Such technology might revolutionize the next generation of long-acting peptide-based medicines.
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pmc
