PURPOSE: The purpose of this paper is to determine the significance of cyclic imide formation of an aspartic acid residue during storage on the pharmaceutical quality of a recombinant human glial cell line-derived neurotrophic factor (rhGDNF) formulation. METHODS: A combination of chromatography, peptide mapping, mass spectroscopy, and protein sequencing was used to purify and characterize the degradation product. Circular dichroism, 1,8-ANS and heparin binding, melting temperature determination, bioassays, and preclinical pharmacokinetic and toxicology testing were performed to examine its equivalence to native rhGDNF. RESULTS: The rhGDNF with cyclic imide at aspartic acid residue 96 showed identical activity, structure, pharmacokinetic profile, and toxicity profile to the native rhGDNF. CONCLUSIONS: Formation of cyclic imide at aspartic acid residue 96 does not affect the pharmaceutical quality of the rhGDNF formulation.
PURPOSE: The purpose of this paper is to determine the significance of cyclic imide formation of an aspartic acid residue during storage on the pharmaceutical quality of a recombinant humanglial cell line-derived neurotrophic factor (rhGDNF) formulation. METHODS: A combination of chromatography, peptide mapping, mass spectroscopy, and protein sequencing was used to purify and characterize the degradation product. Circular dichroism, 1,8-ANS and heparin binding, melting temperature determination, bioassays, and preclinical pharmacokinetic and toxicology testing were performed to examine its equivalence to native rhGDNF. RESULTS: The rhGDNF with cyclic imide at aspartic acid residue 96 showed identical activity, structure, pharmacokinetic profile, and toxicity profile to the native rhGDNF. CONCLUSIONS: Formation of cyclic imide at aspartic acid residue 96 does not affect the pharmaceutical quality of the rhGDNF formulation.
Authors: S Jing; D Wen; Y Yu; P L Holst; Y Luo; M Fang; R Tamir; L Antonio; Z Hu; R Cupples; J C Louis; S Hu; B W Altrock; G M Fox Journal: Cell Date: 1996-06-28 Impact factor: 41.582
Authors: J H Kordower; S Palfi; E Y Chen; S Y Ma; T Sendera; E J Cochran; E J Cochran; E J Mufson; R Penn; C G Goetz; C D Comella Journal: Ann Neurol Date: 1999-09 Impact factor: 10.422
Authors: Mark Cornell Manning; Danny K Chou; Brian M Murphy; Robert W Payne; Derrick S Katayama Journal: Pharm Res Date: 2010-02-09 Impact factor: 4.200