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

Antonella Grigoletto, Anna Mero, Ilenia Zanusso, Oddone Schiavon, Gianfranco Pasut

Research output: Contribution to journalArticle

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. Two different site-specific monoPEGylated forms of hGH are prepared using a chemical, N-terminal PEGylation and enzymatic, transglutaminase-based conjugation approaches. The N-terminal PEGylation yielded a conjugate with a higher thermal stability and, of particular interest, one that is able to recover the secondary structure after thermal denaturation.

Original languageEnglish
Pages (from-to)50-56
Number of pages7
JournalMacromolecular Bioscience
Volume16
Issue number1
DOIs
Publication statusPublished - Jan 1 2016

Keywords

  • enzymatic PEGylation
  • hGH
  • PEGylation
  • transglutaminase

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biomaterials
  • Polymers and Plastics
  • Materials Chemistry

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