Chemical and Enzymatic Site Specific PEGylation of hGH: The Stability and in vivo Activity of PEG-N-Terminal-hGH and PEG-Gln141-hGH Conjugates.
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.
Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Via F. Marzolo 5, 35131, Padua, Italy.
Antonella
A
Grigoletto
Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Via F. Marzolo 5, 35131, Padua, Italy.
Anna
A
Mero
Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Via F. Marzolo 5, 35131, Padua, Italy.
Ilenia
I
Zanusso
Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Via F. Marzolo 5, 35131, Padua, Italy.
Oddone
O
Schiavon
Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Via F. Marzolo 5, 35131, Padua, Italy. gianfranco.pasut@unipd.it.|Veneto Institute of Oncology IOV-IRCCS, 35131, Padua, Italy. gianfranco.pasut@unipd.it.
Gianfranco
G
Pasut
D000818:Animals; D006128:Growth / Q000187:drug effects*; D006207:Half-Life; D019382:Human Growth Hormone / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics / Q000494:pharmacology; D008297:Male; D011092:Polyethylene Glycols / Q000737:chemistry / Q000378:metabolism*; D055550:Protein Stability; D051381:Rats; D011503:Transglutaminases / Q000378:metabolism
D019382:Human Growth Hormone; D011092:Polyethylene Glycols; D011503:Transglutaminases
PEGylation; enzymatic PEGylation; hGH; transglutaminase