Schneider, E.; Hangasky, J.; Ashley, G.; Santi, D. Long-Acting, Longer-Acting and Ultralong-Acting Peptides. Preprints2024, 2024100475. https://doi.org/10.20944/preprints202410.0475.v1
APA Style
Schneider, E., Hangasky, J., Ashley, G., & Santi, D. (2024). Long-Acting, Longer-Acting and Ultralong-Acting Peptides. Preprints. https://doi.org/10.20944/preprints202410.0475.v1
Chicago/Turabian Style
Schneider, E., Gary Ashley and Daniel Santi. 2024 "Long-Acting, Longer-Acting and Ultralong-Acting Peptides" Preprints. https://doi.org/10.20944/preprints202410.0475.v1
Abstract
This perspective describes the current status and future prospects of developing long- to ultralong-acting anti-obesity peptides. First, we review the current status of lipidation, PEGylation, and Fc fusion technologies to obtain long-acting peptides administered once weekly. Next, we describe the approach and current results of using macromolecular peptide prodrugs with pre-programmed releasable linkers to achieve longer-acting peptides that can be administered weekly or monthly. Finally, we posit novel modifications of the latter technology that could provide ultralong half-lives of over one month by advantageously exploiting the clearance rates of released peptides. As examples, we posit that prodrugs of low-clearance GLP-1 agonists derived from peptides already modified by lipidation, PEGylation, and Fc fusion could produce ultralong-acting agonists with dosing intervals reaching 3 to even 6 months.
Biology and Life Sciences, Biology and Biotechnology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
