title: PEGylation of Octreotide Using an α,β-unsaturated-β'-mono-sulfone Functionalized PEG Reagent.
abstract: PEGylation is a well-established technique utilized to overcome the problems related to the therapeutic applications of peptides and proteins. Reasons for the PEGylation of these biological macromolecules include reducing immunogenicity, proteolytic degradation and rapid clearance from blood circulation. Octreotide is an octapeptide analogue of naturally-occurred somatostatin. This peptide has elimination half-life of less than 2 h that requires frequent daily subcutaneous or intravenous administration. To address this issue, octreotide modification was investigated using bis-thiol alkylating PEG reagent. The required bis-thiol alkylating reagent (V) was prepared from commercially available 4-acetyl benzoic acid in five steps. Octreotide disulfide bond was mildly reduced to liberate the two cysteine sulfur atoms followed by bis-alkylation to form PEGylated peptide. The PEG modification process was monitored through the reverse phase HPLC and (1)H-NMR analysis. According to the HPLC chromatograms of PEGylation reaction, the peak with 30 min retention time was identified to be PEG-octreotide. In addition, (1)H-NMR analysis showed a 7.44% degree of PEG substitution.
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Laleh
authors.initials: L
authors.lastname: Erfani-Jabarian
authors.forename: Rasoul
authors.initials: R
authors.lastname: Dinarvand
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Rouini
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Atyabi
authors.forename: Mohsen
authors.initials: M
authors.lastname: Amini
authors.forename: Negar
authors.initials: N
authors.lastname: Mohammadhosseini
authors.forename: Abbas
authors.initials: A
authors.lastname: Shafiee
authors.forename: Alireza
authors.initials: A
authors.lastname: Foroumadi
keywords: Bis-thiol alkylating PEG reagent; Disulfide bond; Octreotide; PEGylation