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

14 Citations (Scopus)

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

Fingerprint

Human Growth Hormone
Hormones
Polyethylene glycols
Pharmacodynamics
Transglutaminases
Hot Temperature
Thermodynamic stability
Proteins
Diaphyses
Denaturation
Pharmacokinetics
Protein Stability
Therapeutic Uses
Thigh
Weight Gain
Rats
Appointments and Schedules
Injections

Keywords

  • enzymatic PEGylation
  • hGH
  • PEGylation
  • transglutaminase

ASJC Scopus subject areas

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

Cite this

Chemical and Enzymatic Site Specific PEGylation of hGH : The Stability and in vivo Activity of PEG-N-Terminal-hGH and PEG-Gln141-hGH Conjugates. / Grigoletto, Antonella; Mero, Anna; Zanusso, Ilenia; Schiavon, Oddone; Pasut, Gianfranco.

In: Macromolecular Bioscience, Vol. 16, No. 1, 01.01.2016, p. 50-56.

Research output: Contribution to journalArticle

Grigoletto, Antonella ; Mero, Anna ; Zanusso, Ilenia ; Schiavon, Oddone ; Pasut, Gianfranco. / Chemical and Enzymatic Site Specific PEGylation of hGH : The Stability and in vivo Activity of PEG-N-Terminal-hGH and PEG-Gln141-hGH Conjugates. In: Macromolecular Bioscience. 2016 ; Vol. 16, No. 1. pp. 50-56.
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