Chemical and Enzymatic Site Specific PEGylation of hGH: The Stability and in vivo Activity of PEG-N-Terminal-hGH and PEG-Gln141-hGH Conjugates

Macromolecular Bioscience
Antonella GrigolettoGianfranco Pasut

Abstract

The use of therapeutic proteins is often impaired by their short in vivo half-lives. PEGylation has been exploited to enhance protein stability and to prolong the pharmacokinetic. The biophysical characterization of two site-specific mono-PEGylated forms of human growth hormone (hGH)--chemically N-terminal PEGylated hGH (PEG-Nter-hGH) and enzymatically Gln141 PEGylated hGH (PEG-Gln141-hGH) via transglutaminase--is outlined here and their pharmacodynamics are compared. The thermal stability of PEG-Nter-hGH was increased with respect to that of hGH and PEG-Gln141-hGH. Pharmacodynamic studies in rats showed that a single injection of the conjugates had a better or comparable potency with respect to a daily hGH on a week schedule in terms of weight gain, femoral length, and tibial diaphysis width.

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Citations

Apr 28, 2016·Expert Opinion on Drug Delivery·Anisha A D'souza, Ranjita Shegokar
Oct 7, 2018·Biological Chemistry·Lukas DeweidHarald Kolmar
Aug 15, 2017·Journal of Drug Targeting·Antonella GrigolettoGianfranco Pasut
May 17, 2017·Pharmaceutical Research·Luca RondaStefano Bettati
Dec 28, 2019·World Journal of Microbiology & Biotechnology·Lovaine DuarteMarco Antônio Záchia Ayub
Mar 7, 2019·International Journal of Endocrinology·Yue ShiJialin Zhang
May 29, 2021·Acta Biomaterialia·Hanmei LiQiang Peng
May 4, 2018·Biomacromolecules·Yanjing Wang, Chi Wu

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